Femoral Vascular Resistance Research Articles

Role of Rho Kinase in Regulating Arterial Stiffness in Anesthetized Rabbits.

The effects of Rho kinase inhibitors fasudil and ripasudil on arterial stiffness were assessed using anesthetized rabbits, where the aortic β and femoral β were measured as a stiffness parameter at each arterial region. Intravenous administration of fasudil and ripasudil dose-dependently decreased blood pressure and femoral vascular resistance and increased femoral arterial blood flow, which appeared according to their in vitro potencies for Rho kinase inhibition. Both drugs increased the aortic β but decreased the femoral β at hypotensive doses. These results suggest that the inhibition of Rho kinase contributes to reducing elastic recoil in the aorta and an increase in compliance in the femoral artery. In addition, the Rho kinase-associated Ca2+-independent mechanism of arterial vascular smooth muscle contraction may be essential in the regulation of femoral arterial stiffness.

Functional symmetry of the aortic baroreflex in female spontaneously hypertensive rats.

Altered baroreflex function is well documented in hypertension; however, the female sex remains far less studied compared with males. We have previously demonstrated a left-sided dominance in the expression of aortic baroreflex function in male spontaneously hypertensive rats (SHRs) and normotensive rats of either sex. If lateralization in aortic baroreflex function extends to hypertensive female rats remains undetermined. This study, therefore, assessed the contribution of left and right aortic baroreceptor afferents to baroreflex modulation in female SHRs. Anesthetized female SHRs (total n = 9) were prepared for left, right and bilateral aortic depressor nerve (ADN) stimulation (1-40 Hz, 0.2 ms, 0.4 mA for 20 s) and measurement of reflex mean arterial pressure (MAP), heart rate (HR), mesenteric vascular resistance (MVR) and femoral vascular resistance (FVR). All rats were also matched for the diestrus phase of the estrus cycle. Reflex (%) reductions in MAP, HR, MVR and FVR were comparable for both left-sided and right-sided stimulation. Bilateral stimulation evoked slightly larger ( P = 0.03) reductions in MVR compared with right-sided stimulation; however, all other reflex hemodynamic measures were similar to both left-sided and right-sided stimulation. These data show that female SHRs, unlike male SHRs, express similar central integration of left versus right aortic baroreceptor afferent input and thus show no laterization in the aortic baroreflex during hypertension. Marginal increases in mesenteric vasodilation following bilateral activation of the aortic baroreceptor afferents drive no superior depressor responses beyond that of the unilateral stimulation. Clinically, unilateral targeting of the left or right aortic baroreceptor afferents may provide adequate reductions in blood pressure in female hypertensive patients.

Differential central integration of left versus right baroreceptor afferent input in spontaneously hypertensive rats.

The blood pressure (BP) regulatory impact of the arterial baroreflex has been well established in health and disease. Under normotensive conditions, we have previously demonstrated functional differences in the central processing of the left versus right aortic baroreceptor afferent input. However, it is unknown if lateralization in aortic baroreflex function remains evident during hypertension. We therefore, investigated the effects of laterality on the expression of baroreflex-driven cardiovascular reflexes in a genetic model of essential hypertension, the spontaneously hypertensive rat (SHR). Anesthetized male SHRs (total n = 9) were instrumented for left, right, and bilateral aortic depressor nerve (ADN) stimulation (1-40 Hz, 0.2 ms, and 0.4 mA for 20 s) and measurement of mean arterial pressure (MAP), heart rate (HR), mesenteric vascular resistance (MVR), and femoral vascular resistance (FVR). Left right, and bilateral ADN stimulation evoked frequency-dependent decreases in MAP, HR, MVR, and FVR. Left and bilateral ADN stimulation evoked greater reflex reductions in MAP, HR, MVR, and FVR compared with right-sided stimulation. Reflex bradycardia to bilateral stimulation was larger relative to both left-sided and right-sided stimulation. Reflex depressor and vascular resistance responses to bilateral stimulation mimicked those of the left-sided stimulation. These data indicate a left-side dominance in the central integration of aortic baroreceptor afferent input. Furthermore, reflex summation due to bilateral stimulation is only evident on the reflex bradycardic response, and does not drive further reductions in BP, suggesting that reflex depressor responses in the SHRs are primarily driven by changes in vascular resistance. Together, these results indicate that lateralization in aortic baroreflex function is not only evident under normotensive conditions but also extends to hypertensive conditions.

PS-B05-3: CARDIOVASCULAR RESPONSES EVOKED BY LOW ENERGY CONTINUOUS VERSUS INTERMITTENT STIMULATION OF THE AORTIC BARORECEPTOR AFFERENTS IN HYPERTENSION

Objectives: Device-based neurostimulation of the carotid baroreceptors is a novel approach to control hypertension. We have previously demonstrated the significance of aortic baroreceptor afferent nerves as a viable alternative neuromodulation target to carotid baroreceptors in lowering mean arterial pressure (MAP) in hypertension. We have also shown that appreciable reductions in MAP do not necessarily require the use of ultrahigh stimulation parameters. In this study, we aimed to investigate if energy consumption for neuromodulation of aortic baroreceptor afferents could be lowered further by using intermittent as opposed to continuous stimulation. Design and method: In male anesthetized spontaneously hypertensive rats (SHRs), the effects of continuous (20 sec) versus intermittent (5 sec ON/3 sec OFF and 5 sec ON/5 sec OFF for 20 sec) stimulation of the left aortic depressor nerve (ADN) on MAP, heart rate (HR), mesenteric (MVR) and femoral (FVR) vascular resistance were assessed using low (5 Hz) and high (15 Hz) frequencies delivered at 0.4 mA and 0.2 ms. Results: Continuous and intermittent low frequency stimulation produced similar sustained decreases in MAP, HR, MVR and FVR. Continuous high frequency stimulation produced larger reductions in MAP, HR, MVR and FVR compared with all low frequency and/or intermittent high frequency stimulations. Conclusions: Low charge intermittent stimulation of the aortic baroreceptor afferents maintains the required reductions in MAP levels in hypertension and intermittent delivery of the electrical stimulus can further lower energy consumption for neuromodulation. Clinically, these findings may provide useful insight for studies using baroreflex modulation in resistant hypertension and other cardiovascular diseases.

Low intensity stimulation of aortic baroreceptor afferent fibers as a potential therapeutic alternative for hypertension treatment

Carotid baroreceptor stimulation has been clinically explored for antihypertensive benefits, but neuromodulation of aortic baroreceptor afferents remains unexplored for potential translation into the clinic. Published studies have used supramaximal stimulations, which are unphysiological and energy inefficient. The objective of the present study was to identify optimal low-charge nerve stimulation parameters that would provide a clinically-relevant (20–30 mmHg) decrease in mean arterial pressure (MAP) in anesthetized spontaneously hypertensive rats. Stimulations of 20 s were delivered to the left aortic depressor nerve (ADN) of these rats using low ranges of pulse amplitudes (≤ 0.6 mA), widths (≤ 0.5 ms) and frequencies (≤ 5 Hz). We also assessed the effects of continuous (20 s) versus intermittent (5 s ON/3 s OFF and 5 s ON/3 s OFF for 20 s) stimulation on MAP, heart rate (HR), mesenteric (MVR) and femoral (FVR) vascular resistance using low (5 Hz) and high (15 Hz) frequencies. Lower pulse amplitudes (0.2 mA) produced 9 ± 2 to 18 ± 2 mmHg decreases in MAP. Higher pulse amplitudes (0.4 mA) produced a median MAP reduction of 28 ± 4 mmHg at 0.2 ms and 5 Hz, with no added benefit seen above 0.4 mA. Continuous and intermittent low frequency stimulation at 0.4 mA and 0.2 ms produced similar sustained decreases in MAP, HR, MVR and FVR. Continuous high frequency stimulation at 0.4 mA and 0.2 ms produced larger reductions in MAP, HR, MVR and FVR compared with all low frequency and/or intermittent high frequency stimulations. We conclude from these findings that “low intensity intermittent” electrical stimulation is an effective alternate way for neuromodulation of the aortic baroreceptor afferents and to evoke a required restoration of MAP levels in spontaneously hypertensive rats. This approach enables low energy consumption and markedly lowers the excessive decreases in MAP and hemodynamic disturbances elicited by continuous high-charge injection protocols.

Sex differences in sympathetic neurovascular and neurohemodynamic relationships during cold pressor test.

Muscle sympathetic nerve activity (MSNA) affects vascular resistance differently in women and men. However, whether this sex difference persists during pronounced increases in MSNA remains unclear. Therefore, the purpose of this study was to examine sex differences in neurovascular transduction during cold pressor test (CPT)-mediated sympathoexcitation. Integrated peroneal MSNA (microneurography) was measured at rest and during a 3-min CPT in young healthy women (n = 11) and men (n = 10). Mean arterial pressure (MAP) was measured beat-by-beat (Finometer), and superficial femoral artery blood flow was measured using duplex ultrasound. Femoral vascular resistance (FVR) was quantified as MAP/femoral blood flow (mmHg/mL/min). Baseline MSNA was similar between women and men (14 ± 9 vs. 15 ± 9 bursts/100 heartbeat, respectively; P = 0.83), whereas MAP was lower (86 ± 7 vs. 92 ± 4 mmHg; P = 0.047), and FVR was greater in women than men (0.54 ± 0.16 vs. 0.36 ± 0.15 mmHg/mL/min; P = 0.02). CPT-induced increases in MSNA were similar between the sexes (19 ± 11 vs. 26 ± 14 bursts/100 heartbeat; P = 0.26) whereas increases in MAP (7 ± 3 vs. 10 ± 3 mmHg; P = 0.03) and FVR (3.2 ± 18.6 vs. 26.8 ± 12.8%; P < 0.01) were smaller in women than in men. Within men, CPT- induced increases in MSNA predicted increases in MAP (R2 = 0.51, P = 0.02) and FVR (R2 = 0.49, P = 0.02). However, MSNA did not predict MAP (R2 = 0.11, P = 0.35) or FVR (R2 = 0.07, P = 0.46) in women. Our findings demonstrate that men experience robust CPT-induced MAP responses that are driven by both neurovascular (MSNA-FVR) and neurohemodynamic (MSNA-MAP) coupling. These relationships were not observed in women, indicating that even during pronounced increases in sympathetic outflow, MSNA is not predictive of vascular nor blood pressure outcomes in young healthy women.

Real-Time Evaluation of Regional Arterial Stiffening, Resistance, and Ocular Circulation During Systemic Administration of Adrenaline in White Rabbits.

PurposeTo evaluate continuous variations of ocular microcirculation by laser speckle flowgraphy and those of regional stiffening by pulse wave velocity (PWV) and vascular resistance under systemic adrenaline administration in rabbits.MethodsSix 16-week-old male rabbits were evaluated. The mean blur rates in the retinal vessel (MBR-RV) and choroid (MBR-CH) were measured. We assessed blood pressure (BP), femoral and carotid vascular resistance, and the heart–ankle (ha)-PWV, heart–femoral (hf)-PWV, and femoral–ankle (fa)-PWV. Adrenaline (100, 300, and 1000 ng/kg) was intravenously administered over a 10-minute period during which the parameters were measured simultaneously every 2 minutes.ResultsThe MBR-RV and MBR-CH values were dose-dependently increased by the adrenaline in parallel with increased BP. At the load of 100 ng/kg adrenaline, the ΔMBR-RV and ΔMBR-CH showed positive correlations with the variation rate in mean arterial blood pressure. Also, the variation rate in carotid vascular resistance and the Δfa-PWV and Δhf-PWV were significantly positively correlated with both the ΔMBR-RV and ΔMBR-CH. At the 300-ng/kg phase, the correlations between the Δha-PWV and both ΔMBR-RV and ΔMBR-CH were canceled; instead, the Δhf-PWV showed a significant negative correlation with the ΔMBR-RV and ΔMBR-CH. At the 1000-ng/kg phase, Δha-PWV again showed significant positive correlations with the ΔMBR-RV and ΔMBR-CH.ConclusionsThese results indicate the possibility that under a systemic administration of adrenaline in rabbits, not only the BP value but also the vascular resistance and arterial function are related to the variation in ocular microcirculation.Translational RelevanceA real-time evaluation system of systemic regional arterial function and ocular microcirculation in rabbits was developed.

Electrical Stimulation of Afferent Lumbar Sympathetic Nerve Impacts Cardio‐Respiratory Functions in Anesthetized Rats

The lumbar sympathetic chains (LSC) contain post-ganglionic vasodilator and vasoconstrictor fibers that control hindlimb vascular tone. The LSC also contain dorsal root ganglion afferent fibers whose roles in cardiorespiratory status remain poorly understood. The objective of the present study was to characterize the cardiorespiratory responses elicited by electrical stimulation (ES) of a LSC in urethane-anaesthetized male Sprague-Dawley rats (n=6) instrumented to measure/calculate mean arterial blood pressure (MAP), femoral artery blood flow (FBF) and femoral vascular resistance (FVR), brachial artery blood flow (BBF), and brachial vascular resistances (BVR), upper airway pressure (UAP), diaphragmatic EMG, respiratory frequency, inspiratory (iTV) and expiratory (eTV) tidal volumes. The right LSC was identified at the level of L4-L6 and a bipolar electrode was placed for ES (5 Hz, 0.5 msec duration, 0.5 mA amplitude for 10 sec). LSC stimulation caused a distinct pattern of cardiorespiratory responses including (a) a 12% decrease in MAP, (b) 15% decrease in ipsilateral FVR, (c) a 10% decrease in BVR (all measured at the peak decrease in MAP), (d) a 15% increase in iVT, (e) a 10% increase in eVT, (f) a15% increase in respiratory frequency, and (g) a 9% increase in diaphragmatic EMG activity. The result of this study demonstrates that ES of afferent fibers within the LSC elicits an array of cardiorespiratory changes in anesthetized rats that would be consistent with preparing the rats for exercise and for flight.

CENTRAL INTEGRATION OF LEFT VERSUS RIGHT BARORECEPTOR AFFERENT INPUT IN FEMALE SPONTANEOUSLY HYPERTENSIVE RATS

Objective: Neuromodulation of blood pressure using baroreflex activation therapy is an effective means to control hypertension in resistant hypertensive patients. In a genetic rat model of essential hypertension, the spontaneously hypertensive rats (SHRs); we were able to demonstrate in male rats that preferential central integration of left baroreceptor afferent input exists relative to that of the right afferents. It remains unknown whether laterality also influences baroreflex responses in female SHRs. Accordingly, the differences in cardiovascular responses triggered by stimulation of the left and right baroreceptor afferents, as assessed by direct electrical stimulation of the aortic depressor nerve (ADN), were studied in female SHRs. Design and method: Pentobarbital-anesthetized female SHRs (25–29 weeks, n = 6–8) were instrumented for left and right ADN stimulation (1–40 Hz, 0.2 ms, 0.4 mA for 20 s) and recording of mean arterial pressure (MAP), heart rate (HR) and mesenteric (MVR) and femoral (FVR) vascular resistance. Female rats were also matched for the diestrus phase of the estrus cycle. Results: Both left and right ADN stimulation resulted in frequency-dependent reductions (P &lt; 0.001) in MAP, HR, MVR and FVR. Reflex reductions in MAP, HR, MVR and FVR were comparable for both left-sided and right-sided stimulation. Conclusions: Unlike males, female SHRs express no differential central modulation of baroreceptor afferent input as evidenced by the comparable left versus right baroreflex-mediated depressor responses. Similar depressor responses in the left versus right stimulation may have been contributed to by the lack of differences in baroreflex-driven changes in HR and vascular resistance. Clinically, targeting either the left or right aortic nerves may equally provide adequate reductions in blood pressure in female hypertensive subjects. Future studies should elucidate the mechanisms responsible for sex differences in the central processing of baroreflex between male and female SHRs.

Increased Serum Klotho With Age-Related Aortic Stiffness and Peripheral Vascular Resistance in Young and Middle-Aged Swine.

The anti-aging function of Klotho gene has been implicated in age-related diseases. The physiological importance of Klotho in the progression of arterial stiffness with aging, however, remains unclear. The goal of this study is to determine the correlation of circulating Klotho with early age-related aortic stiffening and peripheral hemodynamics. We measured serum Klotho levels in a group of pigs with age ranges of 1.5–9 years and investigated the relationship between Klotho levels and biomarkers of aortic stiffening with aging, including aortic pulse wave velocity (PWV), augmentation index (AIx), and pulse pressure (PP). The effects of aortic stiffening on peripheral vascular resistance, compliance, and function were also evaluated. We found that increased aortic stiffness occurred at middle age (>5 years old), as evidenced by an increase in PWV and AIx (p < 0.001), but with no changes in blood pressure and PP. With advancing age, increased femoral vascular resistance positively correlated with aortic PWV and AIx (p < 0.01). No significant difference in endothelium function and arterial compliance for femoral and small peripheral arteries was observed between young and middle-aged groups. The serum Klotho levels were lower in young and higher in middle-aged pigs (p < 0.001), and a positive correlation was found between Klotho and aortic PWV, AIx, and femoral vascular resistance (p < 0.01). Our findings suggest that early-aged aortic stiffening has adverse effect on peripheral hemodynamics, independent of blood pressure levels. Elevated Klotho secretion was associated with increased aortic stiffness and peripheral vascular resistance with aging.

Laterality Influences Central Integration of Baroreceptor Afferent Input in Male and Female Sprague Dawley Rats.

We explored the effects of baroreceptor afferents laterality and sexual dimorphism on the expression of cardiovascular reflex responses to baroreflex activation in Sprague Dawley (SD) rats. Under urethane anesthesia, rats of either sex (total n = 18) were instrumented for left, right and bilateral aortic depressor nerve (ADN) stimulation (1–40 Hz, 0.2 ms, 0.4 mA for 20 s) and measurement of mean arterial pressure (MAP), heart rate (HR) and mesenteric (MVR) and femoral (FVR) vascular resistance. Female rats were matched for the diestrus phase of the estrus cycle. Left, right and bilateral ADN stimulation evoked frequency-dependent drops in MAP, HR, and MVR, and increases in FVR. Irrespective of sex, left and bilateral ADN stimulation as compared to right-sided stimulation mediated greater reflex reductions in MAP, HR, and MVR but not in FVR. In males, reflex bradycardic responses were greater in response to bilateral stimulation relative to both left- and right-sided stimulation. In females, left ADN stimulation evoked the largest increase in FVR. Left and bilateral ADN stimulations evoked greater reductions in MAP and MVR while left-sided stimulation produced larger increases in FVR in females compared with males. All other reflex responses to ADN stimulation were relatively comparable between males and females. These results show a differential baroreflex processing of afferent neurotransmission promoted by left versus right baroreceptor afferent inputs and sexual dimorphism in the expression of baroreflex responses in rats of either sex. Collectively, these data add to our understanding of physiological mechanisms pertaining to baroreflex control in both males and females.

Adult vascular dysfunction in foetal growth-restricted guinea-pigs is associated with a neonate-adult switching in Nos3 DNA methylation.

Foetal growth restriction (FGR) is associated with endothelial dysfunction and cardiovascular diseases in adult subjects. Early vascular remodelling and epigenetic changes occurring on key endothelial genes might precede this altered vascular function. Further, it has been proposed that oxidative stress during development may determine some of these epigenetic modifications. To address this issue, we studied the in vivo and ex vivo vascular function and Nos3 promoter DNA methylation in arteries from eight-month-old guinea-pig born from control, FGR-treated and FGR-NAC-treated pregnancies. Femoral and carotid arteries in vivo vascular function were determined by Doppler, whilst ex vivo vascular function and biomechanical properties were assessed by wire myography. Levels of eNOS mRNA and site-specific DNA methylation in Nos3 promoter in aorta endothelial cells (AEC) were determined by qPCR and pyrosequencing respectively. FGR adult showed an increased femoral vascular resistance (P<.05), stiffness (P<.05) and arterial remodelling (P<.01), along with an impaired NO-mediated relaxation (P<.001). These effects were prevented by maternal treatment with NAC. Endothelial-NOS mRNA levels were decreased in FGR adult compared with control and FGR-NAC (P<.05), associated with increased DNA methylation levels (P<.01). Comparison of Nos3 DNA methylation in AEC showed a differential methylation pattern between foetal and adult guinea-pigs (P<.05). Altogether, these data suggest that adult vascular dysfunction in the FGR does not result from early changes in Nos3 promoter DNA methylation, but from an altered vessel structure established during foetal development.

Peripheral Microvascular Function Reflects Coronary Vascular Function.

Objectives- Coronary endothelial dysfunction is a precursor of atherosclerosis and adverse outcomes. Whether endothelial dysfunction is a localized or generalized phenomenon in humans remains uncertain. We simultaneously measured femoral and coronary vascular function with the hypothesis that peripheral vascular endothelial function will be reflective of coronary endothelial function. Approach and Results- Eighty-five subjects underwent coronary angiography for evaluation of chest pain or abnormal stress tests. Endothelium-dependent and -independent vascular function were measured using intracoronary and intrafemoral infusions of acetylcholine and sodium nitroprusside, respectively. Coronary flow reserve was assessed using intracoronary adenosine infusion. Flow velocity was measured in each circulation using a Doppler wire (FloWire, EndoSonics). Coronary vascular resistance and femoral vascular resistance were calculated as mean arterial pressure (mm Hg)/coronary blood flow (mL/min) and mean arterial pressure (mm Hg)/femoral average peak velocity (cm/s), respectively. Mean age was 53±11 years, 37% were female, 44% had hypertension, 12% had diabetes mellitus, and 38% had obstructive coronary artery disease. There was a correlation between the change in femoral vascular resistance with acetylcholine and acetylcholine-mediated changes in both the coronary vascular resistance ( r=0.27; P=0.014) and in the epicardial coronary artery diameter ( r=-0.25; P=0.021), indicating that subjects with normal endothelial function in the femoral circulation had normal endothelial function in the coronary epicardial and microcirculation and vice versa. The coronary vasodilator response to adenosine also correlated with the femoral vasodilatation with acetylcholine ( r=0.4; P=0.0002). There was no correlation between the coronary and femoral responses to sodium nitroprusside. Conclusions- Endothelial functional changes in the peripheral and coronary circulations were modestly correlated. Thus, peripheral microvascular endothelial function reflects endothelium-dependent coronary epicardial and microvascular function and the coronary flow reserve. Visual Overview- An online visual overview is available for this article.

Age and sex differences in sympathetic and hemodynamic responses to hypoxia and cold pressor test.

Emerging evidence suggests that sympathetic vasoconstriction is lower in young women. We hypothesized that increases in muscle sympathetic nerve activity (MSNA) during acute physiological stressors induce less vasoconstriction in young women compared to young men. Healthy young men (n = 10, 27 ± 1 years), young women (n = 12, 25 ± 1 years), and older women (n = 10, 63 ± 6 years) performed the cold pressor test (hand in ice for 2 min) and continuous hypoxia (10% O2, 90% N2) for 5 min. MSNA, femoral blood flow velocity, heart rate, and blood pressure were acquired continuously. Femoral artery diameter was obtained every minute and used to calculate femoral blood flow, and femoral vascular resistance and conductance. MSNA responses to cold pressor test (P = 0.345) and hypoxia (P = 0.969) were not different between groups. Young women had greater femoral blood flow (P = 0.002) and vascular conductance (P = 0.041) responses to cold pressor test compared with young men. The femoral blood flow response to hypoxia was not different between the two sexes but the increase in femoral flow was attenuated in older women compared with younger women (P = 0.036). These data show that young women had paradoxical vasodilation to cold pressor test. The mechanisms responsible for the attenuated sympathetic vasoconstriction or for enhanced vasodilation in young women during the CPT require further investigation.

Physiological role of nitric oxide for regulation of arterial stiffness in anesthetized rabbits

We assessed effects of acetylcholine and Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME) on the cardio-ankle vascular index (CAVI), an indicator of arterial stiffness from origin of aorta to tibial artery, in halothane-anesthetized rabbits. Acetylcholine decreased the blood pressure, femoral vascular resistance and CAVI, whereas l-NAME did not affect the CAVI at a hypertensive dose. The acetylcholine-induced decrement of CAVI was completely suppressed by l-NAME. These results suggest that the arterial stiffness in rabbits may be independent from homeostatic production of nitric oxide, however, it can be decreased by large amounts of nitric oxide that are intrinsically produced by exogenously administered acetylcholine.

A18700 Differential central modulation of right versus left baroreceptor afferent input in hypertension

Objectives: Baroreflex activation therapy (BAT) is a novel therapy that utilizes electrical field stimulation of the carotid sinus nerve to reduce blood pressure in patients with resistant hypertension. Electrical stimulation of the baroreceptor afferents via the aortic depressor nerve (ADN) in rats may bring new insights into the mechanisms underlying BAT. In this study, we examine cardiovascular responses to electrical stimulation of the left versus right ADN in spontaneously hypertensive rats (SHR). Methods: Male pentobarbital-anesthetized SHRs (25–27 weeks, n = 8–9) were instrumented for right and left ADN stimulation (1–40 Hz, 0.2 ms, 0.4 mA for 20 s) and recording of mean arterial pressure (MAP), heart rate (HR) and mesenteric (MVR) and femoral (FVR) vascular resistance. Results: Both right and left ADN stimulation evoked frequency-dependent (P < 0.001) drops in MAP, HR, MVR and FVR (Fig. 1). However, stimulation of the left ADN evoked greater (P < 0.001) reflex depressor and bradycardic responses and preferential reductions in FVR (hindquarter) over MVR relative to the stimulation of the right side (Fig. 1). Conclusion: Enhanced hypotensive responses to left ADN stimulation are likely due to more potent baroreflex-mediated reductions in HR and vascular resistance relative to the right ADN. These results show a differential central processing of afferent neurotransmission promoted by the left versus right ADN. Clinically, this may have implications in fine-tuning the magnitude of BAT-driven blood pressure drop in patients in relation to the severity and chronicity of hypertension. Further studies are required to understand the mechanisms responsible for differences in the central integration of left versus right afferent input.

Sympathetic Vasoconstriction is Attenuated in Young Women During Hypoxia and Cold Pressor Test

Recent studies suggest that muscle sympathetic nerve activity (MSNA) at rest is correlated to vascular resistance in young men but not in young women. We hypothesized that increases in MSNA during acute physiological stressors induce less vasoconstriction in young women compared to young men. Nineteen healthy humans participated in this study (5 young women, 5 young men, 5 older men, 4 older women). Subjects underwent poikilocapnic hypoxia (5 min, 10% O2, 90% N2) and the cold pressor test (hand in ice water at 0° C for 2 min). MSNA, femoral blood velocity, heart rate, and blood pressure were acquired continuously. Femoral artery diameter was obtained every minute and used to calculate femoral blood flow (FBF) and vascular resistance (FVR). In response to hypoxia, young women had a similar increase in MSNA compared to young men (Δ 6 ± 1 vs. Δ 7 ± 2, bursts/min, P = 0.632) but an exaggerated increase in FBF (Δ 67 ± 10 vs. Δ 32 ± 14 mL/min, P = 0.031) and a greater reduction in FVR (45 ± 4% vs. 24 ± 9%, P = 0.050). In response to cold pressor test, young women had an attenuated rise in MSNA (Δ 5 ± 1 vs. Δ 26 ± 3, bursts/min, P = 0.008) and a smaller increase in FVR (8 ± 17% vs. 173 ± 48%, P = 0.037) compared to young men. Physiological responses to hypoxia and cold pressor test were comparable between older men and women (P &gt; 0.1). These data suggest that young women have decreased sympathetic vasoconstrictor drive during physiological stress, which may explain decreased cardiovascular risk.Support or Funding InformationUL1 TR000127, KL2 TR000126, P01 HL096570, 15PRE24470033

Cardio-ankle vascular index (CAVI) differentiates pharmacological properties of vasodilators nicardipine and nitroglycerin in anesthetized rabbits

Cardio-ankle vascular index (CAVI) has been developed for measurement of vascular stiffness from the aorta to tibial artery, which is clinically utilized for assessing the progress of arteriosclerosis. In this study, we established measuring system of the CAVI in rabbits, and assessed whether the index could reflect different pharmacological actions of nitroglycerin and nicardipine on the systemic vasculature. Rabbits were anesthetized with halothane, and the CAVI was calculated from the well-established basic equations with variables obtained from brachial and tibial blood pressure and phonocardiogram. Nicardipine (1, 3 and 10 μg/kg, i.v.) decreased the blood pressure, femoral vascular resistance, and heart-ankle pulse wave velocity (haPWV). Meanwhile, no significant change was detected in the CAVI at the low or middle dose, which reflects the defining feature of the CAVI that is independent of blood pressure. The index increased at the high dose. Nitroglycerin (2, 4 and 8 μg/kg, i.v.) decreased the blood pressure, femoral vascular resistance, and haPWV. Meanwhile, the CAVI was decreased during the nitroglycerin infusion, which may reflect its well-known pharmacological action dilating conduit arteries. These results suggest that the CAVI differentiates the properties of these vasodilators in vivo.

PP.14.15

Objective: Vasodilators are clinically used in accordance with each pharmacological property. For example, Ca2+ channel blockers are prescribed for patients with hypertension, which dilate arterioles leading to reduction of peripheral vascular resistance. Organic nitrates are used for the treatment of various cardiovascular diseases including angina and heart failure to reduce ventricular preload and afterload, which dilates all segments of the vascular system from large conductance arteries to large veins. Since useful indexes reflecting vascular functions of larger conductance arteries are unavailable using non-invasive methods in contrast to the resistant arteries, we assessed whether the cardio-ankle vascular index (CAVI), established as a marker of arterial stiffness, could reflect different pharmacological actions of nicardipine and nitroglycerin on the systemic vasculature in anesthetized rabbits. Design and method: New Zealand White rabbits were anesthetized with halothane. The CAVI was calculated from the well-established basic equations obtained from the variables of brachial and tibial blood pressure and phonocardiogram. Results: Intravenous administration of nicardipine (1, 3 and 10 μg/kg) decreased the blood pressure, femoral arterial vascular resistance, and heart-ankle pulse wave velocity (haPWV) in a dose-dependent manner. Meanwhile, no significant change was detected in the CAVI at 1 and 3 μg/kg, which reflect the defining feature that CAVI is independent of blood pressure. At the highest dose of 10 μg/kg, the index increased. Intravenous administration of nitroglycerin (2, 4 and 8 μg/kg) also decreased the blood pressure, femoral arterial vascular resistance, and haPWV in a dose-dependent manner. Meanwhile, the CAVI decreased in a dose-dependent manner, which may reflect the pharmacological action that nitroglycerin dilates conductance arteries. Conclusions: These results suggest that CAVI is a useful index that can differentiate pharmacological properties of vasodilators nicardipine and nitroglycerin in anesthetized rabbit.

Functional sympatholysis (FS) in rats is graded with exercise but is not NO‐mediated

FS is the exercise attenuation of sympathetic vasoconstriction. It is unclear if NO is the major mediator of FS or if the size of FS is graded to the level of exercise. Experiments were performed on anaesthetised rats (under UK legislation). Sympathetic vasoconstriction was induced by stimulation of the lumbar sympathetic chain (LSC). EDL contraction was evoked and tension recorded; femoral vascular resistance (FVR) was calculated. Vasoconstriction was evoked during baseline and graded muscle contraction (10–30% max twitch) under control conditions, after NOS inhibition (L‐NAME) and following restoration of baseline (SNP infusion). LSC‐evoked vasoconstriction (an increase in FVR) was attenuated at all levels of muscle contraction. FS was graded and correlated to the peak force at each level. L‐NAME increased baseline FVR and the vasoconstriction, but had no effect on FS at any level of muscle contraction. SNP restored baseline FVR and the vasoconstriction ‐ FS was similar to control conditions. FS was graded to the peak level of muscle contraction, not the force recorded during the sympathetic stimulation per se. Manipulation of endogenous levels of NO changes the magnitude of sympathetic vasoconstriction but does not alter the extent of FS during any of the muscle contractions used. These results are similar to human studies (no role for NO) but differ from animal studies (role for NO; see Saltin et al, 2012).