Similar Blood Pressure Responses Research Articles

Effect of Different Breathing Patterns on Heart Rate and Blood Pressure Response to Resisted Exercises in Females Within the Age Group of 25 to 35 Years

Introduction: Blood pressure and heart rate increases in individuals while performing heavy resisted exercises but acquiring different breathing patterns during exercise shows its effect on blood pressure and heart rate, it may or may not exaggerate. Inhalation or exhalation when coupled with concentric phase of resisted exercise may or may not show similar blood pressure response as compare to inhalation or exhalation when coupled with eccentric phase of resisted exercise whereas Valsalva maneuver can exaggerate the blood pressure response. Objective: To study the inhalation, exhalation and Valsalva maneuver on systolic, diastolic blood pressure and heart rate. Research Design: Quasi experimental. Methodology: 30 female subjects were taken which were asked to do a set of bicep curls with 3 different patterns of breathing with each pattern performed on a separate day. Then the recordings were taken and calculated to see in which pattern of breathing blood pressure and heart rate rises. Result: ANOVA was used and the result showed that diastolic blood pressure increases while exhalation coupled with the concentric phase and inhalation coupled with the eccentric Phase but there is a marked increase in diastolic blood pressure during Valsalva maneuver as compared to the inhalation coupled with the concentric phase and exhalation coupled with the eccentric phase. The result showed that the change in the blood pressure due to the different breathing patterns were significant p>0.05 Conclusion: It is concluded that Valsalva maneuver exaggerates the blood pressure response. Keywords: resisted exercises, Valsalva maneuver, exhalation. breathing patterns.

Adrenal Vein Sampling Results and Surgical Outcomes in Patients with Nonsuppressed Plasma Renin Activity

PurposeTo determine adrenal vein sampling (AVS) and postadrenalectomy outcomes in patients with a nonsuppressed plasma renin activity (PRA) and elevated aldosterone-to-renin ratio (ARR). Materials and MethodsThe study sample included 23 patients with an ARR of >20 and PRA of >1 ng/mL/h (nonsuppressed group) and 69 patients with an ARR of >20 and PRA of <0.6 ng/mL/h (suppressed group) who underwent AVS from 2006 to 2023. Data regarding baseline clinical characteristics, AVS results, and outcomes after adrenalectomy were analyzed. ResultsThe proportion of patients in the nonsuppressed group who had a lateralization index of >4 was lower than that in the suppressed group, although this was nonsignificant (43% vs 62%; P = .15). The mean lateralization index in the nonsuppressed group was lower compared with that in the suppressed group (8.7 vs 17.4; P = .05). The proportion of patients in the nonsuppressed group with improved or cured hypertension following adrenalectomy was similar to that of patients in the suppressed group who also underwent surgery (6/8, 75%, vs 25/32, 78%; P = .71). All hypokalemic patients (32/32) who underwent adrenalectomy had normalization of their potassium levels following procedure. ConclusionsNearly half of patients with nonsuppressed PRA lateralized with AVS. The patients who did lateralize had similar blood pressure response and correction of hypokalemia following adrenalectomy, regardless of PRA. Therefore, patients with a nonsuppressed PRA (>1 ng/mL/h) should still be considered for AVS provided the ARR is elevated.

Impaired vascular β-adrenergic relaxation in spontaneously hypertensive rats: The differences between conduit and resistance arteries

It was suggested that impaired β-adrenergic relaxation in spontaneously hypertensive rats (SHR) might contribute to their high blood pressure (BP). Our study was focused on isoprenaline-induced dilatation of conduit femoral or resistance mesenteric arteries and on isoprenaline-induced BP reduction in SHR and Wistar-Kyoto rats (WKY). We confirmed decreased β-adrenergic relaxation of SHR femoral arteries due to the absence of its endothelium-independent component, whereas endothelium-dependent component of β-adrenergic smooth muscle relaxation was similar in both strains. Conversely, isoprenaline-induced relaxation of resistance mesenteric arteries was similar in both strains and this was true for endothelium-dependent and endothelium-independent components. We observed moderately reduced sensitivity of SHR mesenteric arteries to salmeterol (β2-adrenergic agonist) and this strain difference disappeared after endothelium removal. However, there was no difference in mesenteric arteries relaxation by dobutamine (β1-adrenergic agonist) which was independent of endothelium. The increasing isoprenaline doses elicited similar BP decrease in both rat strains, although BP sensitivity to isoprenaline was slightly decreased in SHR. The blockade of cyclooxygenase (indomethacin) and NO synthase (L-NAME) further reduced BP sensitivity to isoprenaline in SHR. On the other hand, salmeterol elicited similar BP decrease in both strains and the blockade of cyclooxygenase and NO synthase increased BP sensitivity to salmeterol in SHR as compared to WKY. In conclusion, attenuated β-adrenergic vasodilatation of conduit arteries of SHR but similar β-adrenergic relaxation of resistance mesenteric arteries from WKY and SHR and their similar BP response to β-adrenergic agonists do not support major role of altered β-adrenergic vasodilatation for high BP in genetic hypertension.

Adrenal Vein Sampling Results and Surgical Outcomes in Patients with a Normal Plasma Aldosterone Concentration

PurposeTo determine the utility of adrenal vein sampling (AVS) and outcomes after adrenalectomy in patients with normal plasma aldosterone concentration (PAC) and elevated aldosterone-to-renin ratio (ARR). Materials and MethodsThe study sample included 106 patients with ARR greater than 20 and PAC between 5 and 15 ng/dL (normal PAC group) who underwent AVS from 2005 to 2021. These patients were compared with a cohort of 106 patients with ARR >20 and PAC >15 ng/dL (high PAC group) who underwent AVS during the same period. Data regarding baseline clinical characteristics, lateralization indices from AVS, and outcomes after adrenalectomy were analyzed. ResultsAVS was technically successful in 210 patients (210/212, 99%). A smaller proportion of patients in the normal PAC group showed a lateralization index of >4 compared with those in the high PAC group (44% vs 64%, P <.01). A similar proportion of patients in the normal PAC group experienced improved or cured hypertension after adrenalectomy compared with that in the high PAC group (94% vs 88%, P =.31). Hypokalemia was cured in all patients in the normal PAC group after adrenalectomy compared with 98% of patients in the high PAC group (100% vs 98%, P = 1). ConclusionsAlthough lateralization is less frequent for patients with normal PAC, patients who do lateralize show similar blood pressure response and correction of hypokalemia after adrenalectomy, regardless of initial plasma aldosterone levels. Therefore, patients with PAC <15 ng/dL should still be considered for AVS provided the ARR is elevated.

Cell-Specific Actions of the Prostaglandin E-Prostanoid Receptor 4 Attenuating Hypertension: A Dominant Role for Kidney Epithelial Cells Compared With Macrophages.

Background A beneficial role for prostanoids in hypertension is suggested by clinical studies showing nonsteroidal anti-inflammatory drugs, which block the production of all prostanoids, cause sodium retention and exacerbate hypertension. Among prostanoids, prostaglandin E2 and its E-prostanoid receptor 4 receptor (EP4R) have been implicated in blood pressure control. Our previous study found that conditional deletion of EP4R from all tissues in adult mice exacerbates angiotensin II-dependent hypertension, suggesting a powerful effect of EP4R to resist blood pressure elevation. We also found that elimination of EP4R from vascular smooth muscle cells did not affect the severity of hypertension, suggesting nonvascular targets of prostaglandin E mediate this antihypertensive effect. Methods and Results Here we generated mice with cell-specific deletion of EP4R from macrophage-specific EP4 receptor knockouts or kidney epithelial cells (KEKO) to assess the contributions of EP4R in these cells to hypertension pathogenesis. Macrophage-specific EP4 receptor knockouts showed similar blood pressure responses to alterations in dietary sodium or chronic angiotensin II infusion as Controls. By contrast, angiotensin II-dependent hypertension was significantly augmented in KEKOs (mean arterial pressure: 146±3 mm Hg) compared with Controls (137±4 mm Hg; P=0.02), which was accompanied by impaired natriuresis in KEKOs. Because EP4R expression in the kidney is enriched in the collecting duct, we compared responses to amiloride in angiotensin II-infused KEKOs and Controls. Blockade of the epithelial sodium channel with amiloride caused exaggerated natriuresis in KEKOs compared with Controls (0.21±0.01 versus 0.15±0.02 mmol/24 hour per 20 g; P=0.015). Conclusions Our data suggest EP4R in kidney epithelia attenuates hypertension. This antihypertension effect of EP4R may be mediated by reducing the activity of the epithelial sodium channel, thereby promoting natriuresis.

The association of elevated blood pressure during ischaemic exercise with sport performance in Master athletes with and without morbidity

BackgroundAn exaggerated exercise blood pressure (BP) is associated with a reduced exercise capacity. However, its connection to physical performance during competition is unknown.AimTo examine BP responses to ischaemic handgrip exercise in Master athletes (MA) with and without underlying morbidities and to assess their association with athletic performance during the World Master Track Cycling Championships 2019.MethodsForty-eight Master cyclists [age 59 ± 13yrs; weekly training volume 10.4 ± 4.1 h/week; handgrip maximum voluntary contraction (MVC) 46.3 ± 11.5 kg] divided into 2 matched groups (24 healthy MA and 24 MA with morbidity) and 10 healthy middle-aged non-athlete controls (age 48.3 ± 8.3 years; MVC 40.4 ± 14.8 kg) performed 5 min of forearm occlusion including 1 min handgrip isometric contraction (40%MVC) followed by 5 min recovery. Continuous beat-by-beat BP was recorded using finger plethysmography. Age-graded performance (AGP) was calculated to compare race performances among MA. Healthy Master cyclists were further grouped into middle-age (age 46.2 ± 6.4 years; N:12) and old-age (age 65.0 ± 7.7 years; N:12) for comparison with middle-aged non-athlete controls.ResultsHealthy and morbidity MA groups showed similar BP responses during forearm occlusion and AGP (90.1 ± 4.3% and 91.0 ± 5.3%, p > 0.05, respectively). Healthy and morbidity MA showed modest correlation between the BP rising slope for 40%MVC ischaemic exercise and AGP (r = 0.5, p < 0.05). MA showed accelerated SBP recovery after cessation of ischaemic handgrip exercise compared to healthy non-athlete controls.ConclusionOur findings associate long-term athletic training with improved BP recovery following ischaemic exercise regardless of age or reported morbidity. Exaggerated BP in Master cyclists during ischaemic exercise was associated with lower AGP during the World Master Cycling Championships.

Assessment Of Blood Pressure Responses To Various Load Bearing Apparatuses In Law Enforcement Officers

BACKGROUND Recently, some law enforcement agencies have begun transitioning to load bearing vests to help distribute their equipment to reduce hip and back pain from the traditional duty belt. However, no studies have examined other health aspects such as blood pressure of a load bearing vest. PURPOSE: The purpose of this study was to determine if wearing a load bearing vest would alter systolic, diastolic, and mean arterial pressure compared to the traditional duty belt worn by law enforcement officers. METHODS: Twenty one licensed law enforcement officers (mean ± SD, age: 40.5 ± 9.4 years; BMI: 30.3 ± 5.1 kg/m2; VO2 max: 34.5 ± 5.9 ml/kg/min) completed three randomized sets of seated and standing trials for blood pressure a) seated with a weighted utility belt, standing with a weighted utility belt, b) seated with a weighted vest, standing with a weighted vest, c) seated without any apparatus, standing without any apparatus. The weight of the vest and utility belt were 13.6 kg each. RESULTS: Diastolic pressure was higher when seated with a vest, compared to seated with the belt (n = 21, p = .029, +2.6 mmHg). When separating the participants by BMI based on CDC guidelines, increases were observed for standing between normal/overweight (n = 10) and obese (n = 11) for systolic (p = .026, control +14.9 mmHg, belt +11.4 mmHg, vest +8.7 mmHg) and mean arterial pressure (p = .024, control +12.4 mmHg, belt +8.3 mmHg, vest +5.9 mmHg). The normal/overweight group experienced an increase in standing systolic pressure with the belt compared to control (p < .01, +6.7 mmHg). The same group also increased systolic and mean arterial pressures standing with a vest compared to the control trial (p < .01, +10.6 mmHg and 8.4 mmHg) respectively. There were no significant differences in blood pressures within group for obese between the three trials. CONCLUSION: An obese BMI results in a higher systolic and mean arterial pressure when standing compared to a normal/overweight BMI, regardless of apparatus. Both the traditional duty belt and load bearing vest increase standing systolic pressure compared to no apparatus in normal/overweight individuals with no changes for obese individuals. Therefore, both the traditional duty belt and load bearing vest have similar blood pressure responses.

Altered Vascular Reactivity to Circulating Angiotensin II in Familial Hypercholesterolemia.

We have previously shown increased vascular reactivity to angiotensin (Ang) II in familial combined hyperlipidemia. However, this has not been well studied in familial hypercholesterolemia (FH), a condition with incipient endothelial dysfunction. This study aimed to examine microvascular and macrovascular responses to Ang II in FH. Therefore, we investigated the effects of a 3-hour infusion of Ang II on blood pressure and forearm skin microvascular function in 16 otherwise healthy patients with FH and matched healthy controls. Skin microvascular hyperemia was studied by laser Doppler fluxmetry during local heating. Microvascular resistance was determined by the ratio of mean arterial pressure to microvascular hyperemia. Macrovascular reactivity was assessed by changes in brachial blood pressure. Compared with the controls, the FH group had increased baseline systolic blood pressure (127 ± 14 vs. 115 ± 12 mm Hg; P = 0.02), while systolic blood pressure responses were similar (+24 ± 9 vs. +21 ± 7 mm Hg; P = 0.26) after 3 hours of Ang II infusion. At baseline, there were no group differences in microvascular hyperemia or resistance. However, after 3 hours of Ang II infusion, heat-induced microvascular hyperemia was less pronounced in FH (126 ± 95 vs. 184 ± 102 arbitrary units; P = 0.01), while microvascular resistance during heat-induced hyperemia was increased (1.9 ± 0.9 vs. 0.9 ± 0.8, P = 0.01), as compared to controls. Both these responses were further pronounced 1 hour after stopping Ang II. In conclusion, despite similar blood pressure responses to Ang II in the FH group and controls, microvascular dilatation capacity was impaired in the FH group, indicating endothelial dysfunction. These findings and increased microvascular resistance may lead to hypertension and microvascular complications in FH.

Greater muscle strength is associated with reduced autonomic reactivity

We aimed to investigate the autonomic responses to cold pressor test (CPT) in individual with different levels of muscle strength. 57 male subjects participated in the study. Volunteers were divided in tertiles according to their level of relative handgrip strength as Low (LS), Medium (MS) and High (HS). For the CPT the volunteers remained seated in resting for 15 minutes and inserted the right hand in cold water for two minutes. Blood pressure (BP) measurements were taken at rest, during CPT and during recovery. HRV was continuously recorded during the entire protocol. All three groups had similar BP variation, with the values of systolic blood pressure (SBP) increasing during CPT and diminishing during recovery until the third minute. At the first CPT minute LS group showed a substantial increase in low-frequency (LF) activity and a diminished high frequency (HF). LS also presented higher and lower values of LF and HF, respectively, than MS group at the first CPT minute. HS showed an increased vagal activity during recovery. In conclusion, individuals from LS presented similar BP responses to CPT than MS and HS groups but with higher sympathetic activation. HS individuals presented an elevated vagal activity during recovery.

Affective responses to different prescriptions of high-intensity interval exercise in hypertensive patients.

Studies have indicated that high-intensity interval training (HIIT) promotes similar acute reductions on blood pressure (BP) when compared to continuous moderate aerobic exercise. However, it has been associated with lower affective responses to exercise. Therefore, strategies to improve affective responses to exercise are needed. The purpose of this study was to verify the effect of different prescriptions of HIIT on the affective responses of hypertensive elderly women. This is a cross-sectional study. Twenty hypertensive women (65.3±4.2 years) performed four HIIT sessions: 10×1:1 at ±20% of self-selected intensity [SSI] Self20), 10×1:1 at ±30% of SSI (Self30), 10×1:1 at ±40% of SSI (Self40) and an imposed intensity session 5×2-min intervals at 80-85% interspersed with 2-min intervals at 40-50% VO2peak (ImpVO2) and one control session with participants remaining in the sitting position for 28 minutes. Affect response, rating of perceived exertion (RPE) and heart rate (HR) were recorded every five minutes during exercise, and systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR were assessed before and after sessions. The effect of session and moment on the psychophysiological variables was examined by analysis of variance. Affect was lower in the ImpVO2 when compared to SSI sessions. There was no difference in RPE between sessions. The percentage of HRpeak was higher in ImpVO2 compared to SSI sessions. There were no differences in SBP and DBP responses between the sessions. HIIT prescribed based on SSI promoted higher affective responses than HIIT prescribed from 80-85%/40-50% VO2peak with similar BP responses.

Biological Sex Modulates the Adrenal and Blood Pressure Responses to Angiotensin II.

The relationship between biological sex and aldosterone on blood pressure (BP) is unclear. We hypothesized that sex would modify the interaction between aldosterone and vascular responses to salt intake and angiotensin II (AngII). To test this hypothesis, in 1592 subjects from the well-controlled Hypertensive Pathotype cohort, we compared responses of women and men to chronic (BP and aldosterone levels in response to dietary salt) and acute (BP, renal plasma flow, and aldosterone responses to AngII infusion) manipulations. Women had a 30% higher salt sensitivity of BP than men (P<0.0005) regardless of age or hypertension status, a greater BP response to AngII, and a 15% greater aldosterone response to AngII on both restricted and liberal salt diets (P<0.005). Furthermore, there was an interaction (P=0.003) between sex and aldosterone on BP response to AngII. Women also had a greater (P<0.01) increment in renal plasma flow in response to AngII than men. To assess potential mechanisms for this sex effect, we compared aldosterone responses to AngII or potassium from rat zona glomerulosa cells and observed greater aldosterone production in female than male zona glomerulosa cells basally and in response to both agonists (P<0.0001). In a rodent model of aldosterone-mediated cardiovascular disease induced by increased AngII and low NO, circulating aldosterone levels (P<0.01), myocardial damage (P<0.001), and proteinuria (P<0.05) were greater in female than male rats despite having similar BP responses. Thus, increased aldosterone production likely contributes to sex differences in cardiovascular disease, suggesting that women may be more responsive to mineralocorticoid receptor blockade than men.

Renal Nerve Stimulation as Procedural End Point for Renal Sympathetic Denervation.

Renal sympathetic denervation (RDN) as treatment option for hypertension has a strong rationale; however, variable effects on blood pressure (BP) have been reported ranging from non-response to marked reductions in BP. The absence of a procedural end point for RDN is one of the potential factors associated with the variable response. Studies have suggested the use of renal nerve stimulation (RNS) to adequately address this issue. This review aims to provide an overview of the clinical and experimental data available regarding the effects of RNS in the setting of RDN. Animal studies have shown that high-frequency electrical stimulation of the sympathetic nerves in the adventitia of the renal arteries elicits an increase in BP and leads to an increased norepinephrine spillover as a marker of increased sympathetic activity and these effects of stimulation were attenuated or blunted after RDN. In a human feasibility study using RNS both before and after RDN, similar BP responses were observed. Moreover, in patients with resistant hypertension, RNS-induced changes in BP appeared to be correlated with 24-h BP response after RDN. These data suggest that RNS is a useful tool to identify renal sympathetic nerve fibers in patients with treatment-resistant hypertension undergoing RDN, and to predict the likely effectiveness of RDN treatments. In acute procedural settings both in animal and human models, RNS elicits increase in BP and HR before RDN and these effects are blunted after RDN. Up to now, there is preliminary evidence that the RNS-induced BP changes predict 24-h ABPM outcome at follow-up in patients with resistant hypertension. Of note, studies are small sized and results of large trials comparing conventional RDN to RNS-guided RDN are warranted.

Simulating a virtual population's sensitivity to salt and uninephrectomy.

Salt sensitivity, with or without concomitant hypertension, is associated with increased mortality. Reduced functional renal mass plays an important role in causing salt-sensitive hypertension for many individuals. Factors that are important in the condition of decreased renal mass and how they affect blood pressure (BP) or salt sensitivity are unclear. We used HumMod, an integrative mathematical model of human physiology, to create a heterogeneous population of 1000 virtual patients by randomly varying physiological parameters. We examined potential physiological mechanisms responsible for the change in BP in response to high-salt diet (8× change in salt intake for three weeks) with full kidney mass and again after the removal of one kidney in the same group of virtual patients. We used topological data analysis (TDA), a clustering algorithm tool, to analyse the large dataset and separate patient subpopulations. TDA distinguished five unique clusters of salt-sensitive individuals (more than 15 mmHg change in BP with increased salt). While these clusters had similar BP responses to salt, different collections of variables were responsible for their salt sensitivity, e.g. greater reductions in glomerular filtration rate (GFR) or impairments in the renin-angiotensin system. After simulating uninephrectomy in these virtual patients, the three most salt-sensitive clusters were associated with a blunted increase in renal blood flow (RBF) and higher increase in loop and distal sodium reabsorption when compared with the salt-resistant population. These data suggest that the suppression of sodium reabsorption and renin-angiotensin system is key for salt resistance, and RBF in addition to GFR may be an important factor when considering criteria for kidney donors. Here, we show that in our model of human physiology, different derangements result in the same phenotype. While these concepts are known in the experimental community, they were derived here by considering only the data obtained from our virtual experiments. These methodologies could potentially be used to discover patterns in patient sensitivity to dietary change or interventions and could be a revolutionary tool in personalizing medicine.

OP.7B.01] MASKED HYPERTENSIVES EXHIBIT AN EXAGGERATED BLOOD PRESSURE RESPONSE DURING HANDGRIP EXERCISE SIMILAR TO THAT IN HYPERTENSIVE INDIVIDUALS

Objective: Masked hypertension has been associated with increased risk for target organ damage and cardiovascular disease. Recent evidence indicate that hypertensive individuals exhibit exaggerated blood pressure (BP) response during exercise and delayed recovery, linked to excessive sympathetic stimulation and an overactive exercise pressor reflex. Whether individuals with masked hypertension (masked-HYP) also exhibit exaggerated BP and systemic vascular resistance (SVR) responses as true hypertensives (true-HYP) during exercise has not been investigated. Therefore, the aim of this study was to evaluate the cardiovascular responses during handgrip exercise and recovery in masked-HYP, true-HYP, and normotensive (NORMO) individuals. Design and method: Eighty six individuals participated in the present study: healthy-NORMO (n = 28), masked-HYP (n = 27), and true-HYP (n = 31). All hypertensive participants were newly diagnosed, untreated, with no other known cardiovascular disease. Following a complete history, physical examination, and blood testing, office and ambulatory BP were measured in order to determine their hypertensive status. All participants underwent an exercise protocol, consisting of a 3-min rest (baseline), a 3-min handgrip exercise at 30% maximal voluntary contraction (MVC), and a 3-min recovery. Beat-by-beat BP and heart rate (HR) were continuously assessed via photoplethysmography (Finapress) throughout the protocol and SVR was calculated. Results: There were no differences among the three groups in age, smoking status, body mass index, fasting blood glucose, lipid profile, and MVC. Masked-HYP exhibited similar baseline BP to NORMO, however, during HG-exercise, masked-HYP exhibited a markedly greater (p < 0.05) systolic/diastolic BP response compared with NORMO (174.8 ± 13.5/98.5 ± 7.0 vs. 159.2 ± 15.7/91.3 ± 9.2 mmHg, respectively) and similar BP responses to true-HYP (181.4 ± 14.5/101.8 ± 9.5 mmHg). In addition, during exercise, masked-HYP exhibited a significant increase in SVR (p < 0.05), similar to that observed in true-HYP, whereas no significant increase in SVR was observed in NORMO. During the 3-min post-exercise period, BP in masked-HYP declined and returned to values comparable to those in NORMO (p = 0.32). Conclusions: This is the first study to show that during isometric exercise, masked-HYP exhibit exaggerated BP and SVR responses, suggesting an overactive exercise pressor reflex in masked hypertension. The cardiovascular responses during exercise in masked-HYP are similar to those in true-HYP.

Abstract P335: Greater Reduction in Sympathetic Tone following ET B Receptor Blockade in Rats Lacking the Clock Gene Bmal1 during High Salt Diet

The absence of diurnal oscillations in blood pressure is associated with increased cardiovascular morbidity and mortality. The clock gene Bmal1 plays important roles in diurnal cardiovascular control as mice lacking Bmal1 have lower blood pressure and lack a diurnal rhythm. Our lab has previously reported a global Bmal1 knockout rat model that lacks a night-day difference in sodium excretion. Due to the importance of endothelin signaling in sodium homeostasis and autonomic tone, we sought to characterize the hemodynamic and autonomic responses of our Bmal1 knockout (KO) rat to high salt diet and endothelin receptor blockade. Male rats homozygous for the Bmal1 mutation (KO, n = 4) and wild type (WT, n = 7) littermate controls were implanted with telemetry transmitters to record blood pressure. After a recovery period of at least one week, the rats were placed on 7 days each of normal salt (0.49% NaCl) diet, high salt (4.0% NaCl) diet, followed by high salt diet containing the specific ET B receptor antagonist A192621 (10 mg/kg/day, p.o.). Rats were placed in metabolic cages for the last three days of each diet. Surprisingly, KO rats had a similar night-day difference in mean arterial pressure (MAP) as WT during normal salt diet (6.3 ± 0.4 vs. 6.9 ± 0.9 mmHg; respectively), high salt diet (7.1 ± 0.1 vs. 5.4 ± 0.9 mmHg; respectively), and high salt + A192621 (5.4 ± 0.4 vs. 4.8 ± 1.1 mmHg; respectively). KO and WT rats had similar 24-hr MAP during normal salt diet (104.1 ± 3.3 vs. 107.3 ± 1.2 mmHg; respectively), high salt diet (113.8 ± 4.1 vs. 114.0 ± 1.4 mmHg; respectively), and high salt + A192621 (136.3 ± 8.6 vs. 133.4 ± 3.1 mmHg; respectively). Despite these similar blood pressure responses to high salt diet and ET B antagonism, KO rats had a significantly greater reduction in vasomotor sympathetic to parasympathetic tone compared to WT rats as demonstrated by low frequency to high frequency (LF/HF) analysis of diastolic blood pressure variability (-0.9 ± 0.3 vs. 0.1 ± 0.2 ΔLF/HF relative to normal salt; respectively; p = 0.01). These results indicate that lack of Bmal1 may result in greater ET B receptor mediated vasomotor sympathetic tone in rats fed a high salt diet and that factors other than Bmal1 may be influential in circadian control of blood pressure in rats.

Physiological Sensitivity to Salt and Uninephrectomy

Salt sensitivity, with or without concomitant hypertension, is associated with increased mortality. Reduced functional renal mass plays an important role in causing salt sensitive hypertension for many individuals but the mechanisms are unclear. Moreover, different derangements in human physiology can result in the same phenotype. Methodologies that could discover patterns in sensitivity to dietary change or interventions would be a revolutionary tool in personalizing medicine. We used HumMod, an integrative mathematical model of human physiology, to simulate population responses to changes in salt intake with or without reduced kidney mass (uninephrectomy). A heterogeneous population of 1000 virtual patients was created by randomly varying important physiological parameters. We examined potential physiological mechanisms responsible for the chronic blood pressure (BP) response to salt (8‐fold change in salt intake for 3 weeks) with full kidney mass and again with a single kidney in the same group of virtual patients. We also used topological data analysis (TDA), a new clustering algorithm tool, to separate patient subpopulations. In the entire population, BP increased with increased salt intake (14 ± 3 mmHg). This was associated with small changes in glomerular filtration rate (GFR) but significant increases in renal blood flow, total peripheral resistance, and distal tubular sodium reabsorption. Interestingly, TDA distinguished 5 unique clusters of salt sensitive individuals (&gt; 15 mmHg change in BP with increased salt). While these clusters had similar BP responses to salt, they were significantly different in the mechanisms of salt sensitivity (e.g. greater reductions in GFR or impairments in the renin angiotensin system.) After kidney removal in these same individuals, the three most salt sensitive clusters were associated with a blunted increase in renal blood flow (RBF), exaggerated increases in loop and distal sodium reabsorption, and greater sodium and volume retention as compared to the salt resistant population. These data suggest that the suppression of sodium reabsorption and renin angiotensin system is key for salt resistance, while RBF in addition to GFR may be an important factor when considering criteria for potential kidney donors.Support or Funding InformationSupported by NSF EPS‐0903787, P20 GM104357, and NIH PO1 HL51971.

Chlorthalidone Versus Amlodipine for Hypertension in Kidney Transplant Recipients Treated With Tacrolimus: A Randomized Crossover Trial

Chlorthalidone is a very effective antihypertensive drug, but it has not been studied prospectively in kidney transplant recipients with hypertension. Recent data indicate that calcineurin inhibitors activate the thiazide-sensitive sodium chloride cotransporter, providing further rationale to test thiazides in this population. Randomized noninferiority crossover trial (noninferiority margin,-2.8mmHg). Hypertensive kidney transplant recipients using tacrolimus (median duration, 2.4 years after transplantation; mean estimated glomerular filtration rate, 63±27 [SD] mL/min/1.73m2; mean systolic blood pressure [SBP], 151±12mmHg). Amlodipine (5-10mg) and chlorthalidone (12.5-25mg) for 8 weeks (separated by 2-week washout). Average daytime (9 am to 9 pm) ambulatory SBP. Blood pressure and laboratory parameters. 88 patients underwent ambulatory blood pressure monitoring, of whom 49 (56%) with average daytime SBP>140mmHg were enrolled. 41 patients completed the study. Amlodipine and chlorthalidone both reduced ambulatory SBP after 8 weeks (mean changes of 150±12 to 137±12 [SD] vs 151±12 to 141±13mmHg; effect size,-4.2 [95% CI,-7.3 to 1.1] mmHg). Despite these similar blood pressure responses, chlorthalidone reduced proteinuria by 30% (effect size,-65 [95% CI,-108 to-35] mg/g) and also reduced physician-assessed peripheral edema (22% to 10%; P<0.05 for both). In contrast, chlorthalidone temporarily reduced kidney function and increased both serum uric acid and glycated hemoglobin levels. Open-label design, short follow-up, per-protocol analysis. Chlorthalidone is an antihypertensive drug equally effective as amlodipine after kidney transplantation.

Low-frequency stimulation of group III and IV hind limb afferents evokes reflex pressor responses in decerebrate rats.

Contraction of freely perfused hind limb muscles in decerebrate rats evokes the exercise pressor reflex, resulting in sympathetic activation and increased blood pressure. This reflex is propagated along mechanically sensitive group III and metabolically sensitive group IV afferent nerve fibers. Recent research by our laboratory has focused on the exaggeration of the exercise pressor reflex in decerebrate rats with simulated peripheral artery disease, which was induced by ligating the femoral artery for 72 h before the start of the experiment. Recently, we showed that ligating the femoral artery increased the responses of single fiber group III and IV triceps surae muscle afferents to static contraction. The objective of this study was to determine if electrical stimulation of group III and IV afferents at frequencies approximating those occurring during static contraction was capable of reflexively increasing arterial blood pressure. We directly stimulated muscle afferents in the absence of muscle contraction for both freely perfused and ligated rats. We established 0.25 Hz as the minimal stimulation frequency to observe a sustained blood pressure response. The blood pressure response increased in a graded fashion as both stimulus frequency and motor threshold were increased. Additionally, we observed similar blood pressure responses from both freely perfused and ligated rats, suggesting that spinal and medullary processing of group III and IV afferent input plays no role in augmenting the pressor response to contraction caused by femoral artery ligation.

BR 05-2 ANGIOPLASTY OF ATHEROSCLEROTIC RENAL ARTERY STENOSIS

Abstract Atherosclerotic renal artery stenosis is an increasingly recognized medical problem especially in elderly patients. It commonly occurs with systemic manifestations including hypertension (HTN), chronic kidney disease (CKD) or atherosclerotic diseases including coronary or peripheral artery disease. Significant renal artery stenosis may result in HTN, ischemic nephropathy, however it is still in debate about the benefit of revascularization. Although several randomized controlled trials including Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) and Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study has failed to reveal a significant benefit of angioplasty, angioplasty with medical therapy is increasingly accepted in some patients with certain clinical conditions.For determining appropriate candidates for renal artery angioplasty, anatomical evaluation of renal artery stenosis and atherosclerotic change of abdominal aorta should be preferentially undergone. Angiographic stenosis more than 50% with physiologic significance, or ≥70% stenosis is considered significant. Translesional pressure gradient with or without hyperemia should be routinely assessed in intermediate stenosis (50-70%). Intravascular ultrasound assessment may be used to evaluate luminologic severity or characteristics.Global renal ischemia caused by renal artery stenosis should be an appropriate indication of revascularization, however unilateral and solitary ischemia would be considerable. Patients with cardiac disturbance syndrome or pulmonary edema relevant to renal artery stenosis can be managed with renal artery angioplasty. Several prospective randomized trials have failed to show a significant difference in blood pressure (BP) response after revascularization or medical treatment, nevertheless resistant HTN with global renal ischemia would be a proper indication of revascularization. Both patient groups with revascularization and medication alone in CORAL showed similar BP response about 15 mmHg. Such BP responders with optimal medication may be not appropriate candidates for revascularization for controlling BP. Patients with reduced renal function and global renal ischemia may be also good candidates for renal artery stenting. However, evidences to support revascularization in unilateral renal artery stenosis are limited. Revascularization would be considered if renal artery stenosis is relevant to hemodynamic significance. Although revascularization with stenting have been commonly used for patients with renal artery stenosis, previous results are inconclusive and lacking to support comprehensive indications of current clinical application. Selection of candidates who benefits with angioplasty should be carefully conducted with sufficient diagnostic evaluation.

Abstract P029: Vendor Specific Differences in the Sprague Dawley Rat Strain Alter Baseline Blood Pressure and Body Composition and Influence the Impact of Slow Fetal Growth on Later Cardiovascular Risk

Low birth weight is associated with increased risk for cardiovascular (CV) disease including hypertension in later life. We previously reported that reduced uterine perfusion (RUP) in timed pregnant Sprague Dawley (SD) dams purchased from Harlan induced intrauterine growth restriction (IUGR) associated with hypertension and enhanced sensitivity to angiotensin II (Ang II) in male rats at 4 months of age. In addition, male IUGR exhibited a two-fold increase in testosterone relative to control. Upon castration, hypertension and sensitivity to Ang II were abolished suggesting that programmed CV risk is testosterone dependent in the male IUGR. The aim of this study was to determine if vendor differences in the SD strain impact CV risk following a developmental insult. Timed pregnant SD rats were purchased from Charles River and underwent either RUP or sham surgery at day 14 of gestation. Birth weight was significantly reduced in IUGR relative to control (P&lt;0.05). At 4 months of age, body weight remained significantly decreased in male IUGR relative to control, blood pressure did not differ when measured in conscious, chronically instrumented animals, and male control and IUGR from Charles River also exhibited a similar blood pressure response to acute Ang II. However, baseline blood pressures were higher in male control from Charles River versus blood pressure previously noted for male control from Harlan. Thus, these results suggest that vendor specific differences in the SD rat strain influence baseline CV risk and effect the developmental programming of CV risk following slow fetal growth.