Higher Blood Pressure Increase Research Articles

Increased Oxygen Saturation in Retinal Venules During Isometric Exercise Is Accompanied With Increased Peripheral Blood Flow in Normal Persons.

A recent study has shown that an increase in the arterial blood pressure of approximately 10 mm Hg in healthy persons can increase the oxygen saturation in venules from the retinal periphery but not from the macular area. The purpose of the present study was to investigate whether a higher increase in blood pressure has further effects on oxygen saturations and whether this is accompanied with changes in retinal blood flow. In 30 healthy persons, oxygen saturation, diameter, and blood flow were measured in arterioles to and venules from the retinal periphery and the macular area. The experiments were performed before and during an experimental increase in arterial blood pressure of (mean ± SD) 18.3 ± 6.2 mm Hg. A higher number of venules than arterioles branching from the temporal vascular arcades to the macular area was balanced by a smaller diameter of the venules. Isometric exercise induced significant contraction of both peripheral and macular arterioles (P<0.01 for both comparisons) and significant increase in oxygen saturation in both peripheral and macular venules (P<0.001 for both comparisons). This was accompanied with a significant increase in the blood flow in the peripheral arterioles and venules (P=0.4 for both comparisons), but not in their macular counterparts (P>0.06 for both comparisons). Increased systemic blood pressure leading to arterial contraction and increased venous oxygen saturation in the retina in normal persons can increase peripheral blood flow without significant effects on macular blood flow. This may contribute to explaining regional differences in the response pattern of retinal vascular disease.

Trends in associations between socioeconomic development and urban-rural disparity with high blood pressure in Chinese children and adolescents over two decades.

This study aimed to assess the association between the trend of urban-rural disparity in high blood pressure (HBP) in Chinese children and adolescents and socioeconomic development. Data on 1,054,602 students aged 7-18 years were obtained from five successive national surveys administered in 29 Chinese provinces in 1995, 2000, 2005, 2010, and 2014. HBP was defined as average measured systolic BP and/or diastolic BP equal to or more than 95th percentile. The socioeconomic indicators at the provincial-level included gross domestic product (GDP) per capita, the Engel coefficient, and urbanization rates. From 1995 to 2014, HBP prevalence in Chinese children and adolescents fluctuated between 6.9% and 9.2%. Rural areas had a higher prevalence of HBP than urban areas, with a diminishing trend in urban-rural disparity from 1995 to 2010 with a reduced OR from 1.45 (95% CI: 1.40-150) in 1995 to 1.09 (1.05-1.12) in 2010, whereas a widening gap in 2014 with OR of 1.23 (1.19-1.26)). A positive association existed between the improvement of socioeconomic indicators and the increase in HBP, which was demonstrated obviously by the Engel coefficient strata. The increases in the urbanization rates were accompanied by a greater increase of HBP in urban than in rural areas. The large urban-rural disparity suggests a priority of HBP control in rural children due to their current and future HBP and cardiovascular disease risks. Socioeconomic development could affect the urban-rural disparity in HBP risk, reflecting the importance of effective policy responses for preventing HBP by avoiding unhealthy lifestyles brought about by rapid economic development.

Dynamic changes in metabolic health status in Chinese adults: Multiple population-based surveys in Shanghai, China.

Aims/introductionMetabolic syndrome (MS) has been increasing worldwide. The secular change in MS components, however, remains unclear. This study aimed to examine the dynamic change in metabolic health status in Chinese adults.Materials and methodsThree population‐based surveys using multistage stratified sampling were performed in Chinese aged 35–74 years in Shanghai in 2002–2003 (n = 12,302), 2009 (n = 7,400), and 2017 (n = 19,023). MS was defined according to the Adult Treatment Panel III criteria for Asian‐Americans. Generalized Estimating Equations and Cochran‐Armitage Trend Test was used to assess the prevalence trend over the years.ResultsThe prevalence of MS doubled in Chinese adults over the period (P for trend < 0.001). The largest increase occurred in younger men. Among MS components, the prevalence of high waist‐circumference (HWC), high blood glucose (HBG) and high blood pressure (HBP) increased in all subjects, whereas the prevalence of high triglycerides (HTG) and low high‐density lipoprotein cholesterol (LHC) increased in men but decreased in women. The increase in HBP contributed most to elevated MS, followed by HBG and HWC, resulting in the HBP‐HBG‐HWC the most common cluster of MS components. Metabolically unhealthy overweight also grew over the period.ConclusionsMetabolic health status has been exacerbating in Chinese adults and may increase burden of non‐communicable diseases.

Fixed-dose combinations in the treatment of hypertension to increase adherence

Despite a wide range of antihypertensive drugs, blood pressure (BP) control often remains unsatisfactory, and every year the number of people with uncontrolled high BP increases. One of the strategies aimed at improving medical adherence is the use of fixed-dose combinations of 2 antihypertensive drugs for starting therapy, and, if necessary, 3 drugs. Initiation of therapy with 2 drugs in one tablet is recommended for most patients. A review of algorithms for choosing combinations of antihypertensive drugs in different clinical situations, including in patients with various comorbid conditions, is presented. Simplification of treatment regimens makes it possible to choose the most optimal solutions in various clinical situations, in particular, with stage I-II hypertension, with a combination of hypertension with chronic kidney disease, as well as with a combination of hypertension with coronary artery disease and a number of other diseases.

Effect of self-initiated and fully-automated self-measurement on blood pressure

Self-measurement of blood pressure (BP) is regularly used to diagnose hypertension and to monitor BP at home. We recently showed that self-measurement of BP may elicit a pressor or 'auto-cuff' response. In this study we examined whether the pressor response is different between self-initiated and fully-automated BP measurement. We performed two randomized crossover studies in outpatients visiting a hypertension clinic. The first cohort of 52 participants performed six unattended self-initiated and six fully-automated BP measurements, while continuously monitoring BP and central haemodynamics using finger photoplethysmography. The second cohort consisted of 120 patients who performed three self-initiated and three fully-automated BP measurements. In the first cohort (mean age 61.2 ± 10.4 years, mean office BP 142.0 ± 19.9/82.5 ± 12.2 mmHg, 36.7% female) average systolic and diastolic BP increased by 7.3 ± 8.5/3.3 ± 4.0 mmHg in the group with self-initiated BP measurements, while BP increased by 3.3 ± 6.3/1.4 ± 3.0 mmHg during fully-automated measurements (p = 0.002/p = 0.002 for difference between groups). The higher BP increase during self-initiated BP measurements resulted from an increase in heart rate and cardiac output. In the second cohort (mean age 58.0 ± 14.1 years, mean office BP 153.6 ± 23.8/86.3 ± 14.0 mmHg, 44.1% female) self-initiated BP measurement resulted in a 2.1 ± 6.8/0.9 ± 4.0 mmHg higher systolic and diastolic BP compared with fully-automated self-measurement (p = 0.001/0.018). In conclusion, our findings suggest that self-initiated BP measurement using a fully-automated method results in a more reliable BP compared with a self-initiated semi-automated method by attenuating the auto-cuff response. These findings may have implications for the self-measurement of BP.

The correlation studies between ambulatory blood pressure and OSA in non-hypertensive patients

Objective:To discuss the changes and rules of nighttime blood pressure in obstructive sleep apnea(OSA) patients without hypertension.Method:Eighty-nine non-hypertensive patients whose office blood pressure was lower than 130/85 mmHg and diagnose with OSA by PSG in sleep monitoring room were choose as the research group.Forty non-hypertensive and polyp of vocal cord or vocal nodules patients whose office blood pressure was lower than 130/85 mmHg and diagnose with non-OSA by PSG were choose as matched group.All the patients were in treatment in our hospital from December 2017 to June 2018. All the patients got PSG,and the same time got the ambulatory blood pressure monitoring based on pulse transit time all night.Compared the mean value of systolic blood pressure,the mean value of diastolic blood pressure.Higher than 12 mmHg blood pressure rise index,the mean rise in blood pressure. The highest increase in blood pressure, maximum systolic pressure between the study group and the marched group all night.Result:The difference of all the test index between the study group and the marched group was significant(P<0.05).In OSA patients.The difference of all the test index between the severe OSA group and the mild OSA group or the moderate OSA group was significant(P<0.05).In severe OSA group.The difference between the fluctuation of blood pressure caused by respiratory events and spontaneous blood pressure fluctuation was significant(P=0.004).The difference of the mean value of diastolic blood pressure(P=0.032) blood pressure rise index(P=0.037) the mean rise in blood pressure(P=0.045) between age 55 or older patients and under 55years old patients.Conclusion:Ambulatory blood pressure monitoring synchronizatied in PSG contribute to the early diagnosis and prevention of hypertension in OSA patients.

Hypertension is associated with increased age at the onset of psoriasis and a higher body mass index in psoriatic disease.

High blood pressure (HBP) is a common comorbidity in psoriatic disease. Some studies indicate a higher prevalence of HBP among arthritis patients, in relation to psoriasis alone, within the psoriatic spectrum. Our objective was to study the prevalence of HBP in both types of patients as well as to analyse the factors associated with it. A cross-sectional observational study of 600 patients with psoriatic disease attended in a multidisciplinary clinic of a reference centre. We first analysed the frequency of this comorbidity and then the factors associated with it using conditional logistic regression. The significant factors in this first model were introduced in a multivariate model using a backward step approach. A total of 144 patients were hypertensive (24%). Of patients with arthritis, 86/290 (29.7%) had HBP, compared with 58/310 (18.7%) with psoriasis (OR 1.7 95%, CI 1.25-2.50, p = 0.003). Hypertension was independently associated with higher age at onset of psoriasis (OR 1.04, 95%CI 1.03-1.06, p < 0.001) and a higher body mass index (OR 1.13, 95%CI, 1.06-1.22, p < 0.001). HBP is more prevalent in patients with arthritis within the spectrum of psoriatic disease. Patients with a higher body mass index and those with later-onset psoriasis are more prone to this comorbidity. • The factors of psoriatic disease associated with HBP are little known. • HBP is more prevalent in patients with arthritis within the spectrum of psoriatic disease. • In patients with psoriatic disease, for each point of increase in the body mass index, the risk of HBP increases by 13%. • For each year of onset of psoriasis above 40years, the risk of HBP increases by 4%.

Genetic predisposition to salt-sensitive normotension and its effects on salt taste perception and intake.

Salt sensitivity is an independent CVD and mortality risk factor, which is present in both hypertensive and normotensive populations. It is genetically determined and it may affect the relationship between salt taste perception and salt intake. The aim of this study was to explore the genetic predisposition to salt sensitivity in a young and a middle-aged adult population and its effects on salt taste perception and salt intake. The effects of Na loading on blood pressure (BP) were investigated in twenty normotensive subjects and salt sensitivity defined as the change in BP after 7 d of low-Na (51·3 mmol Na/d) and 7 d of high-Na diet (307·8 mmol Na/d). Salt taste perception was identified using the British Standards Institution sensory analysis method (BS ISO 3972:2011). Salt intake was assessed with a validated FFQ. DNA was genotyped for SNP in the SLC4A5, SCNN1B and TRPV1 genes. The subjects with AA genotype of the SLC4A5 rs7571842 exhibited the highest increase in BP (∆ systolic BP=7·75 mmHg, P=0·002, d=2·4; ∆ diastolic BP=6·25 mmHg, P=0·044, d=1·3; ∆ mean arterial pressure=6·5 mmHg, P=0·014, d=1·7). The SLC4A5 rs10177833 was associated with salt intake (P=0·037), and there was an association between salt taste perception and salt sensitivity (r s 0·551, P=0·041). In conclusion, there is a genetic predisposition to salt sensitivity and it is associated with salt taste perception. The association between salt taste perception and discretionary salt use suggests that preference for salty taste may be a driver of salt intake in a healthy population and warrants further investigation.

TRPV4 (Transient Receptor Potential Vanilloid 4) Channel-Dependent Negative Feedback Mechanism Regulates Gq Protein-Coupled Receptor-Induced Vasoconstriction.

Several physiological stimuli activate smooth muscle cell (SMC) GqPCRs (Gq protein-coupled receptors) to cause vasoconstriction. As a protective mechanism against excessive vasoconstriction, SMC GqPCR stimulation invokes endothelial cell vasodilatory signaling. Whether Ca2+ influx in endothelial cells contributes to the regulation of GqPCR-induced vasoconstriction remains unknown. Ca2+ influx through TRPV4 (transient receptor potential vanilloid 4) channels is a key regulator of endothelium-dependent vasodilation. We hypothesized that SMC GqPCR stimulation engages endothelial TRPV4 channels to limit vasoconstriction. Using high-speed confocal microscopy to record unitary Ca2+ influx events through TRPV4 channels (TRPV4 sparklets), we report that activation of SMC α1ARs (alpha1-adrenergic receptors) with phenylephrine or thromboxane A2 receptors with U46619 stimulated TRPV4 sparklets in the native endothelium from mesenteric arteries. Activation of endothelial TRPV4 channels did not require an increase in Ca2+ as indicated by the lack of effect of L-type Ca2+ channel activator or chelator of intracellular Ca2+ EGTA-AM. However, gap junction communication between SMCs and endothelial cells was required for phenylephrine activation or U46619 activation of endothelial TRPV4 channels. Lowering inositol 1,4,5-trisphosphate levels with phospholipase C inhibitor or lithium chloride suppressed phenylephrine activation of endothelial TRPV4 sparklets. Moreover, uncaging inositol 1,4,5-trisphosphate profoundly increased TRPV4 sparklet activity. In pressurized arteries, phenylephrine-induced vasoconstriction was followed by a slow, TRPV4-dependent vasodilation, reflecting activation of negative regulatory mechanism. Consistent with these data, phenylephrine induced a significantly higher increase in blood pressure in TRPV4-/- mice. These results demonstrate that SMC GqPCR stimulation triggers inositol 1,4,5-trisphosphate-dependent activation of endothelial TRPV4 channels to limit vasoconstriction.

The effects of passive leg raising and ultrafiltration stopping on blood pressure in hemodialysis patients.

Hemodialysis-associated hypotension, one of the more serious issues in hemodialysis patients, can be treated by passive leg raising (PLR) and ultrafiltration (UF) stopping. We investigated the effects of PLR and UF stopping on blood pressure in hemodialysis patients. The study was conducted in 76 end-stage renal disease patients. After the second hour of dialysis, systolic and diastolic blood pressure (SBP and DBP) of the patients who did not develop intradialytic hypotension (IDH) were measured in the supine position. Thereafter, PLR was performed by raising the legs 20°; and after 3min, SBP and DBP were measured again. UF was then stopped in the PLR position; SBP and DBP were repeated 3min later. The same procedure was performed during IDH in the patients that developed IDH. A mean 5-mmHg (p<0.05) increase in SBP and a mean 2-mmHg increase in DBP (p<0.05) were observed by PLR in the supine position. UF stopping during PLR increased SBP by a mean of 1mmHg (p<0.05) while no change was observed in DBP (p=ns). IDH occurred in 19 (25%) patients. PLR positioning increases SBP and DBP by a mean of 8mmHg (p<0.05) and 3mmHg (p<0.05), respectively, in the supine position during IDH. During IDH, UF stopping in the PLR position did not significantly increase SBP and DBP in patients as compared to the PLR position. SBP and DBP increase during PLR. UF stopping during PLR does not lead to a higher increase in blood pressure as compared to PLR positioning.

Regadenoson in Myocardial Perfusion Study - First Institutional Experiences in Bosnia and Herzegovina.

Introduction:Myocardial perfusion imaging (MPI) is widely used in the evaluation of known and suspected coronary artery disease (CAD). Imaging of heart in stress and rest enables the comparison of myocardial uptake of radiotracer in proportion to the needs and coronary flow, which is used for detection of perfusion defects. Exercise stress and pharmacologic agents are used for the stressing purpose. Novel pharmacologic stressor regadenoson is A2A selective adenosine agonist, which selectively binds to the adenosine receptors in coronary arteries causing coronary dilatation.Materials and methods:We analyzed 50 myocardial perfusion studies performed with regadenoson as a pharmacologic agent that was injected before Tc99m-sestamibi in stress imaging. Stress and rest sets of images were evaluated for relative uptake of Tc99m-sestamibi in order to detect and characterize perfusion defects. After the injection of regadenoson, hemodynamic parameters and potential side-effects were closely monitored. Side-effects were stratified per severity as mild, moderate and severe. Studies were read by nuclear medicine physicians using quantitative perfusion SPECT software. Additional diagnostic information such as wall motion and wall thickening were provided by gating.Results:Thirty-three patients (66%) experienced one or more side-effects upon the administration of regadenoson, most commonly warmth and chest discomfort. In all patients but one (98%), the symptoms were mild, of short duration and self-limiting. Out of all side-effects registered, 44 (96%) were mild, and 2 (4%) were moderate. Two moderate side-effects developed in one patient with a prior history of asthma, and included shortness of breath and cough. Heart rate changed by 16 +- 31 bpm. Highest increase in blood pressure was 30 mm Hg for systolic, and 10 mm Hg for diastolic. One case of significant decrease in blood pressure was noted from the hypertensive basal values, 50 mm for systolic, and 30 mm Hg for diastolic. ST segment depression of up to 1 mm occurred in 4 cases (8%), and T-wave changes in 3 cases (6%). No conduction abnormalities, significant hypotension, symptomatic bradycardia or cardiac arrest ocurred.Conclusion:Our first institutional experiences proved regadenoson as A2A selective adenosine agonist as a pharmacologic stressor to be safe, tolerable and easily used. Its safety profile enabled the study to be performed in patients with respiratory disease also.

Central Autonomic Dysfunction Delays Recovery of Fingolimod Induced Heart Rate Slowing.

BackgroundIn multiple sclerosis (MS) patients, Fingolimod may induce prolonged heart-rate slowing which might be caused by MS-related central autonomic lesions.ObjectivesTo evaluate whether MS-patients with prolonged heart-rate slowing (> six hours) upon Fingolimod show cardiovascular-autonomic dysfunction before Fingolimod-initiation.MethodsBefore Fingolimod-initiation, we recorded electrocardiographic RR-intervals (RRIs) and blood-pressure (BP) at rest, upon standing-up, during metronomic deep-breathing, Valsalva-maneuver, and “sustained-handgrip-exercise” in 21 patients with relapsing-remitting MS, and 20 healthy persons. We calculated sympathetic and parasympathetic cardiovascular parameters, including low- (LF) and high-frequency (HF) powers of RRI- and BP-oscillations, RRI-RMSSDs, RRI- and BP-changes during handgrip-exercise, parasympathetic heart-rate-slowing in relation to BP-overshoot after Valsalva-strain-release. We compared values of healthy persons and patients with and without prolonged heart-rate slowing after Fingolimod-initiation (ANOVA; significance: p<0.05).ResultsUpon Fingolimod-initiation, 7/21 patients had prolonged HR-slowing. Before Fingolimod, these patients had higher resting BP and higher BP increase during handgrip-exercise than had the other participants (p<0.05). They did not reduce parasympathetic HR-parameters upon standing-up. After Valsalva-strain-release, their parasympathetic HR-slowing in response to BP-overshoot was four times higher than in the other participants (p<0.05).ConclusionsThe autonomic cardiovascular dysfunction in MS-patients with delayed HR-re-acceleration upon Fingolimod-initiation suggests that MS-related central autonomic lesions compromise HR-re-acceleration upon Fingolimod.Trial RegistrationGerman Clinical Trial Register DRKS00004548 http://drks-neu.uniklinik-freiburg.de/drks_web/setLocale_EN.do

Association between body size and blood pressure in children from different ethnic origins

ObjectiveTo assess associations between body size and blood pressure in children (5-6 years) from different ethnic origins.MethodFive ethnic groups of the ABCD cohort were examined: Dutch (n=1 923), Turkish (n=99), Moroccan (n=187), Black-African (n=67) and Black-Caribbean (n=121). Data on body-mass-index (BMI), waist-to-height ratio (WHtR), fat-mass-index (FMI), and systolic blood pressure (SBP) and diastolic blood pressure (DBP), were collected. Linear regression analysis with restricted cubic splines was used to examine non-linear associations between body size and blood pressure, adjusted for age, sex, height and birth weight.ResultsEthnic differences were found in associations of BMI with SBP and DBP (SBP: p=0.001 and DBP: p=0.01) and FMI with SBP (p=0.03). BMI and FMI had a relatively large positive association with SBP in Turkish children (BMI: β=2.46mmHg; 95%CI:1.20-3.72; FMI: β=2.41mmHg; 95%CI:1.09-3.73) compared to Dutch (BMI: β=1.31mmHg; 95%CI:0.71-1.92; FMI: β=0.84mmHg; 95%CI:0.23-1.45). Black-Caribbean and Moroccan children showed high blood pressure with low BMI and FMI. Moroccan children showed higher SBP with high BMI and FMI. WHtR was positively associated with SBP and DBP, similar in all ethnic groups. Generally, strongest associations with blood pressure were found for BMI in all ethnic groups.ConclusionEthnic-specific associations between BMI, and FMI and blood pressure are present at young age, with Turkish children showing the highest increase in blood pressure with increasing body size. The higher blood pressure in the Black-Caribbean and Moroccan children with low BMI needs further research. WHtR or FMI do not seem to be associated more strongly to blood pressure than BMI in any ethnic group.

Does High Blood Pressure Increase Perceived Healthiness of Foods with Sodium Claims on the Label?

This study measured Canadian consumers’ perceived clarity of the wording and the healthiness perception of food products carrying different types of claims related to sodium and examined the effect of having high blood pressure (BP) on these perceptions. Online panellists (n=803) were randomly assigned to one of four identical mock canned soup labels carrying the same Nutrition Facts table, differing only by the claim on the label: 1) nutrient content (NC), 2) function claim, 3) disease risk reduction (DRR) claim, or 4) ‘tastes great’ claim acting as a control. Overall, panellists, regardless of BP, rated the NC claim as the most clear, while the function claim was found to be the least clear (p&lt;0.001). DRR and taste claims were intermediate. Despite the NC claim being the most clear, participants perceived the product with the DRR claim as the healthiest, and all 3 sodium claims were perceived healthier than the taste claim (p&lt;0.001). Those with high BP (n=226) consistently rated all products with sodium related claims healthier compared to those with normal BP (p=0.02); furthermore products with sodium claims, irrespectively of the type, were perceived as healthier than the one with the taste claim. This study demonstrates that, although clarity was rated similarly irrespective of BP, having high BP increases the perceived healthiness of products carrying claims mentioning sodium. Supported by: AFMNet; CIHR STIHRGrant Funding Source : AFMNet; CIHR Strategic Training Program in Public Health Policy (CW); University of Toronto McHenry Chair (ML)

Monosodium glutamate is related to a higher increase in blood pressure over 5 years: findings from the Jiangsu Nutrition Study of Chinese adults

One large cross-sectional study across four countries suggests that glutamate intake may be inversely associated with blood pressure (BP). The aim of this analysis was to investigate a possible association between monosodium glutamate (MSG) intake and change in blood pressure over 5 years. Data from 1227 Chinese men and women who participated in the Jiangsu Nutrition Study (JIN) were analyzed. In this study, MSG intake and blood pressure were quantitatively assessed in 2002, and followed-up in 2007. MSG intake was associated with a significant increase in SBP and DBP. A strong sex interaction was observed in relation to SBP change. Women with high MSG intake were more likely to have increased SBP and DBP. Total glutamate intake was also positively associated with an increase in SBP. In those chronically taking antihypertensive medications, there was a strong association between MSG intake and an increase in DBP. MSG intake may have independent BP-increasing effects, especially among women and those taking hypertension medications at baseline and follow-up.

THE EFFECT OF REPEATED ANTISENSE THERAPY ON VARIOUS VASOACTIVE SYSTEMS IN YOUNG REN-2 TRANSGENIC RATS: PP.29.140

Objective: We demonstrated that single injection of antisense oligodeoxynucleotides (AS) against AT1 receptor had transient antihypertensive effect in TGR. We were interested whether repeated AS therapy will have durable effect on blood pressure (BP) and on the contribution of principle vasoactive systems to BP regulation in this model of ANG II-dependent hypertension. Methods: From the age of 30 days heterozygous Ren-2 rats were injected in 10-day intervals with AS until the age of 60 days. On days 40, 50 and 70 of age, basal BP and acute responses to consecutive blockade of renin-angiotensin (10 mg/kg captopril), sympathetic (5 mg/kg pentolinium) and nitric oxide (NO) (30 mg/kg L-NAME) systems were determined in conscious rats. Results: AS therapy decreased BP and reduced cardiac hypertrophy. Both these effects disappeared after the third AS injection. Captopril-induced BP decrease was higher on day 70 in untreated than in AS-treated TGR, suggesting higher contribution of RAS in established hypertension. On the contrary, AS therapy decreased the contribution of sympathetic system on day 40 (during hypertension development). BP decrease was double after SNS than after RAS blockade. AS-treated animals had higher BP increase after NO blockade on day 40. The impact of NO on BP control increased with age, suggesting its role as a compensatory mechanism against augmented activity of pressor systems. The dependency of principle vasoactive systems on the number of renin gene copies was evaluated in three groups of animals: HanSD (-/-),TGR heterozygous for renin gene (+/−) and homozygous TGR (+/+). The contribution of angiotensin-dependent and nifedipine-sensitive vasoconstriction increased with the number of renin gene copies, while heterozygous and homozygous TGR had reduced NO vasodilatory component. Conclusions: Repeated AS therapy of Ren-2 TGR has transient antihypertensive effect, which correlates with cardiac hypertrophy. Augmented sympathetic activity together with reduced NO activity contribute to hypertension in initial phases, while increased RAS influence prevails in established hypertension.

Mineralocorticoid receptor activation contributes to salt-induced hypertension and renal injury in prepubertal Dahl salt-sensitive rats

Excessive prepubertal salt intake permanently increases blood pressure (BP). We examined the role that the mineralocorticoid receptor (MR) plays in the salt-induced hypertension and renal damage of prepubertal Dahl salt-sensitive (SS) rats. Prepubertal (6 weeks old) and adult (10 weeks old) Dahl SS rats fed a high (8.0%) salt (HS) diet for 10 weeks were compared in terms of BP and renal function. The effect of treatment between the ages of 4 and 10 weeks with the MR antagonist eplerenone (0.125% in chow), the vasodilator hydralazine (50 mg/kg/day in drinking water) or the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (tempol) (0.6 mmol/kg/day in drinking water) on the BP and renal function of prepubertal rats fed a HS diet for 10 weeks was also examined. Excessive salt intake starting in prepuberty was associated with a higher BP increase and greater proteinuria than if it started in adulthood. Eplerenone moderately reduced BP and markedly improved renal injury during its administration in prepubertal rats. These effects continued after drug discontinuation. Hydralazine greatly decreased BP and reduced proteinuria, but these effects were completely lost after drug discontinuation. Excessive salt increased urinary 8-hydroxy-2'-deoxyguanosine levels, intrarenal macrophage infiltration and renal plasminogen activator inhibitor-1 and transforming growth factor-beta mRNA expression. Eplerenone, but not hydralazine, attenuated these salt-induced inflammatory reactions. Tempol improved salt-induced hypertension and renal injury, even after its discontinuation. Dahl SS rats exposed to excessive salt in prepubescence show a permanent increase in susceptibility to salt-induced hypertension and proteinuria. MR activation may promote these effects at least in part by inducing oxidation and inflammation.

Dynamic pressure–flow relationship of the cerebral circulation during acute increase in arterial pressure

The physiological mechanism(s) for the regulation of the dynamic pressure-flow relationship of the cerebral circulation are not well understood. We studied the effects of acute cerebral vasoconstriction on the transfer function between spontaneous changes in blood pressure (BP) and cerebral blood flow velocity (CBFV) in 13 healthy subjects (30 +/- 7 years). CBFV was measured in the middle cerebral artery using transcranial Doppler. BP was increased stepwise with phenylephrine infusion at 0.5, 1.0 and 2.0 microg kg(-1) min(-1). Phenylephrine increased BP by 11, 23 and 37% from baseline, while CBFV increased (11%) only with the highest increase in BP. Cerebrovascular resistance index (BP/CBFV) increased progressively by 6, 17 and 23%, demonstrating effective steady-state autoregulation. Transfer function gain at the low frequencies (LF, 0.07-0.20 Hz) was reduced by 15, 14 and 14%, while the phase was reduced by 10, 17 and 31%. A similar trend of changes was observed at the high frequencies (HF, 0.20-0.35 Hz), but gain and phase remained unchanged at the very low frequencies (VLF, 0.02-0.07 Hz). Windkessel model simulation suggests that increases in steady-state cerebrovascular resistance and/or decreases in vascular compliance during cerebral vasoconstriction contribute to the changes in gain and phase. These findings suggest that changes in steady-state cerebrovascular resistance and/or vascular compliance modulate the dynamic pressure-flow relationship at the low and high frequencies, while dynamic autoregulation is likely to be dominant at the very low frequencies. Thus, oscillations in CBFV are modulated not only by dynamic autoregulation, but also by changes in steady-state cerebrovascular resistance and/or vascular compliance.

Epinephrine Is Required for Normal Cardiovascular Responses to Stress in the Phenylethanolamine N-Methyltransferase Knockout Mouse

Epinephrine (EPI) is an important neurotransmitter and hormone. Its role in regulating cardiovascular function at rest and with stress is unclear, however. An epinephrine-deficient mouse model was generated in which the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase was knocked out (KO). Blood pressure and heart rate were monitored by telemetry at rest and during graded treadmill exercise. Cardiac structure and function were evaluated by echocardiography in mice under 1 of 2 conditions: unstressed and lightly anesthetized or restrained and awake. In KO mice, resting cardiovascular function, including blood pressure, heart rate, and cardiac output, was the same as that in wild-type mice, and the basal norepinephrine plasma level was normal. However, inhibition of sympathetic innervation with the ganglion blocker hexamethonium caused a 54% smaller decrease in blood pressure in KO mice, and treadmill exercise caused an 11% higher increase in blood pressure, both suggesting impaired vasodilation in KO mice. Interestingly, phenylethanolamine N-methyltransferase KO did not change the heart rate response to ganglionic blockade and exercise. By echocardiography, KO mice had an increased ratio of left ventricular posterior wall thickness to internal dimensions but did not have cardiac hypertrophy, suggesting concentric remodeling in the KO heart. Finally, in restrained, awake KO mice, heart rate and ejection fraction remained normal, but cardiac output was significantly reduced because of diminished end-diastolic volume. Our data suggest that epinephrine is required for normal blood pressure and cardiac filling responses to stress but is not required for tachycardia during stress or normal cardiovascular function at rest.

Differential blood pressure and heart rate responses to supramedullary brain stimulation in cats.

The purpose of this study was to compare the cardiovascular responses to electrical stimulation of different supramedullary brain regions. Arterial blood pressure (BP) and heart rate (HR) effects were elicited by electrical stimulation of the lateral hypothalamus (LH), mamillary bodies (Mm), substantia nigra (SN), globus pallidus (GP), and the subthalamic nucleus (Sub) in conscious, freely moving cats. Pressor responses were obtained from all of these regions. The higher intensity of stimulation the higher increase in BP and HR was obtained. However, clear-cut differences occurred in the effects both during and after the termination of stimulations. Namely, a continuous increase in BP and HR was obtained from the LH and SN. In contrast, the initial increase in BP and HR was followed by a reduction compared to the peak value of the effects of stimulation in the GP and the Sub. However, the BP and HR never reduced to the pre-stimulaion level during the stimulation. Also the changes following the cessation of stimulation at the different brain loci were dissimilar. The BP and HR either returned gradually to the pre-stimulation level, or long-lasting oscillation occurred. The electrical activity of the nucleus of the solitary tract (NTS) and the vagus nerve co-varied with the changes in BP and HR. It is concluded that the supramedullary stimulations produce differential cardiovascular effects, and these effects are modified by the baroreflexes that are activated by the electrically elicited rise in blood pressure.