scholarly journals Postmenopausal hypertension: role of the sympathetic nervous system in an animal model

2014 ◽  
Vol 306 (4) ◽  
pp. R248-R256 ◽  
Author(s):  
Rodrigo O. Maranon ◽  
Roberta Lima ◽  
Mohammed Mathbout ◽  
Jussara M. do Carmo ◽  
John E. Hall ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Female Rats ◽  
Renal Nerves ◽  
Adrenergic Blockade ◽  
Sympathetic Activation ◽  
Young Females ◽  
Sympathetic Nervous ◽  
Old Females

In postmenopausal women the mechanisms responsible for hypertension have not been completely elucidated, and there are no gender-specific guidelines for women despite studies showing that blood pressure is not as well controlled to goal in women as in men. In the present study we tested the hypotheses that the sympathetic nervous system and the renal sympathetic nerves contribute to hypertension in aging female rats, that sympathetic activation may be mediated by the melanocortin 3/4 receptor (MC3/4R), and that MC3/4R activation may be due to increases in leptin. α-1, β-1,2-Adrenergic blockade reduced blood pressure in both young (3–4 mo) and old (18–19 mo) female spontaneously hypertensive rats (SHR). Renal denervation attenuated the hypertension more in old females than young females. MC3/4R antagonism with SHU-9119 given intracerebroventricularly had no effect on blood pressure in either young or old females but significantly reduced blood pressure in old males. Plasma leptin levels were similar in old male and female SHR and in old versus young females. These data suggest that the hypertension in old female SHR is in part due to activation of the sympathetic nervous system, that the renal nerves contribute to the hypertension, and that the mechanism responsible for sympathetic activation in old females is independent of the MC3/4R.

scholarly journals Roles for the sympathetic nervous system, renal nerves, and CNS melanocortin-4 receptor in the elevated blood pressure in hyperandrogenemic female rats

2015 ◽  
Vol 308 (8) ◽  
pp. R708-R713 ◽  
Author(s):  
Rodrigo Maranon ◽  
Roberta Lima ◽  
Frank T. Spradley ◽  
Jussara M. do Carmo ◽  
Howei Zhang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Female Rats ◽  
Elevated Blood Pressure ◽  
Renal Nerves ◽  
Female Rat ◽  
Elevated Blood ◽  
Melanocortin 4 Receptor ◽  
Sympathetic Nervous

Women with polycystic ovary syndrome (PCOS) have hyperandrogenemia and increased prevalence of risk factors for cardiovascular disease, including elevated blood pressure. We recently characterized a hyperandrogenemic female rat (HAF) model of PCOS [chronic dihydrotestosterone (DHT) beginning at 4 wk of age] that exhibits similar characteristics as women with PCOS. In the present studies we tested the hypotheses that the elevated blood pressure in HAF rats is mediated in part by sympathetic activation, renal nerves, and melanocortin-4 receptor (MC4R) activation. Adrenergic blockade with terazosin and propranolol or renal denervation reduced mean arterial pressure (MAP by telemetry) in HAF rats but not controls. Hypothalamic MC4R expression was higher in HAF rats than controls, and central nervous system MC4R antagonism with SHU-9119 (1 nmol/h icv) reduced MAP in HAF rats. Taking a genetic approach, MC4R null and wild-type (WT) female rats were treated with DHT or placebo from 5 to 16 wk of age. MC4R null rats were obese and had higher MAP than WT control rats, and while DHT increased MAP in WT controls, DHT failed to further increase MAP in MC4R null rats. These data suggest that increases in MAP with chronic hyperandrogenemia in female rats are due, in part, to activation of the sympathetic nervous system, renal nerves, and MC4R and may provide novel insights into the mechanisms responsible for hypertension in women with hyperandrogenemia such as PCOS.

scholarly journals Contribution of Sympathetic Nervous System to High Blood Pressure in Salt Hypertensive Dahl Rats

2021 ◽  
pp. 117-118
Author(s):  
Josef Zicha
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Salt Intake ◽  
Adrenergic Blockade ◽  
Control Groups ◽  
Adrenergic Mechanisms ◽  
Salt Hypertension ◽  
Sympathetic Nervous

The important participation of sympathetic nervous system in various forms of experimental hypertension is well known. This is also true for salt hypertension elicited by excess salt intake in Dahl salt-sensitive rats (for review see Zicha et al. 2012). Two recent studies in Dahl rats (Zicha et al. 2019, Puleo et al. 2020) evaluated the hypothesis on the role of β-adrenergic WNK4-NCC pathway in salt-sensitive hypertension which has been proposed by Mu et al. (2011). Although these studies differed in many experimental details, both of them demonstrated a major importance of α1- rather than β adrenergic mechanisms for the development of salt hypertension in this rat strain. Zicha et al. (2019) demonstrated that chronic β adrenergic blockade by propranolol did not lower blood pressure (BP) in Dahl salt-sensitive rats developing salt hypertension. It also did not modify their sympathetic component or natriuretic response to acute hydrochlorothiazide administration which inhibited the activity of sodium-chloride cotransporter (NCC). Puleo et al. (2020) reported that chronic β-adrenergic blockade failed to affect salt hypertension development or to reduce renal WNK4-NCC pathway. On the other hand, their study demonstrated the important influence of α1 adrenergic pathway on the activity, expression and phosphorylation of NCC. Chronic α1-adrenergic antagonism by terazosin treatment in Dahl salt-sensitive rats, which started before the onset of high salt intake, considerably attenuated the development of salt hypertension. This treatment diminished BP difference between the salt-loaded Dahl salt-sensitive rats and their control groups by 70-75 %. However, terazosin-treated Dahl salt-sensitive animals fed a high-salt diet had not only suppressed renal NCC activity but they also did not respond to acute phenylephrine administration. This suggests that chronic α1-adrenergic blockade affected both renal sodium retention mechanisms and α1-adrenergic vasoconstriction (Puleo et al. 2020). It remains to determine how these two mechanisms contribute to salt hypertension in Dahl rats. We found that the acute ganglionic blockade lowered substantially BP of salt hypertensive Dahl rats, abolishing 45-55 % of the BP difference between salt-loaded Dahl salt-sensitive rats and their control groups (Zicha et al. 2019). If we consider the results of both above studies, it seems that the renal contribution might be responsible for about 25 % of BP elevation seen in Dahl salt-sensitive rats developing salt hypertension, whereas α1-adrenergic vasoconstriction contributes to this BP change by about 50 %. Of course, this consideration is highly speculative. Nevertheless, it might stimulate further effort to distinguish the role of kidney and brain in the pathogenesis of salt hypertension. Perhaps even more promising could be the estimation of renal and extrarenal effects of central sympathoexcitation in Dahl rats (Mark 1991, Gabor and Leenen 2012, Fujita et al. 2009) which is related to central α2-adrenergic mechanisms (Wainford et al. 2015). As far as the role of kidney in the pathogenesis of salt hypertension is concerned (Frame et al. 2019), some attention should also be paid to participation of renal vascular and tubular effects of increased sympathetic tone in these salt hypertensive animals.

scholarly journals SPECULATIONS ОN BLOOD PRESSURE INCREASE MECHANISMS IN RENAL ARTERY CLIPPED WISTAR RATS

2013 ◽  
Vol 19 (3) ◽  
pp. 221-226
Author(s):  
N. V. Kuzmenko ◽  
M. G. Pliss ◽  
N. S. Rubanova ◽  
V. A. Tsyrlin
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Renal Artery ◽  
Renovascular Hypertension ◽  
Wistar Rats ◽  
Renal Denervation ◽  
Renal Nerves ◽  
Blood Pressure Elevation ◽  
Sympathetic Nervous

Objective.To examine the mechanisms underlying the activation of the sympathetic nervous system and blood pressure elevation in vasorenal hypertension in the male Wistar rats weighing 250–300 g.Design and methods.We observed the development of renovascular hypertension, beat-to-beat interval and heart rate variability in animals with intact renal nerves and denervated ischemic kidney for 8 weeks after renal artery clamping. Eight weeks later after renal artery clamping in hypertensive rats with denervated ischemic kidney, both-sided renal denervation was performed, and blood pressure was monitored for 6 weeks.Results.Although the ischemic kidney denervation reduces the activity of the sympathetic nervous system, it does not prevent renovascular hypertension development. However, both-sided renal denervation leads to the normalization of blood pressure in the rats with stable renovascular hypertension.Conclusion.We suggest that increased afferent fl ow from structural formations of the ischemic kidney plays an important role for the increased sympathetic nervous system activity.

Acute elevation of plasma non-esterified fatty acids increases pulse wave velocity and induces peripheral vasodilation in humans in vivo

2007 ◽  
Vol 113 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Niels P. Riksen ◽  
Marlies Bosselaar ◽  
Stephan J.L. Bakker ◽  
Robert J. Heine ◽  
Gerard A. Rongen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Pulse Wave Velocity ◽  
Wave Velocity ◽  
Adenosine Receptor ◽  
Pulse Wave ◽  
Adenosine Receptor Antagonist ◽  
Sympathetic Nervous ◽  
Control Infusion

Plasma NEFA (non-esterified fatty acid) concentrations are elevated in patients with obesity. In the present study we first aimed to provide an integral haemodynamic profile of elevated plasma NEFAs by the simultaneous assessment of blood pressure, pulse wave velocity, FBF (forearm blood flow) and sympathetic nervous system activity during acute elevation of NEFAs. Secondly, we hypothesized that NEFA-induced vasodilation is mediated by adenosine receptor stimulation. In a randomized cross-over trial in healthy subjects, Intralipid® was infused for 2 h to elevate plasma NEFAs. Glycerol was administered as the Control infusion. We assessed blood pressure, pulse wave velocity, FBF (using venous occlusion plethysmography) and sympathetic nervous system activity by measurement of noradrenaline and adrenaline. During the last 15 min of Intralipid®/Control infusion, the adenosine receptor antagonist caffeine (90 μg·min−1·dl−1) was administered into the brachial artery of the non-dominant arm. Compared with Control infusion, Intralipid® increased pulse wave velocity, SBP (systolic blood pressure) and pulse pressure, as well as FBF (from 1.8±0.2 to 2.7±0.6 and from 2.3±0.2 to 2.7±0.6 ml·min−1·dl−1 for Intralipid® compared with Control infusion; P<0.05, n=9). Although in a positive control study caffeine attenuated adenosine-induced forearm vasodilation (P<0.01, n=6), caffeine had no effect on Intralipid®-induced vasodilation (P=0.5). In conclusion, elevation of plasma NEFA levels increased pulse wave velocity, SBP and pulse pressure. FBF was also increased, either by baroreflex-mediated inhibition of the sympathetic nervous system or by a direct vasodilating effect of NEFAs. As the adenosine receptor antagonist caffeine could not antagonize the vasodilator response, this response is not mediated by adenosine receptor stimulation.

scholarly journals Role of Sympathetic Nervous System in Cyclosporine-Induced Rise in Blood Pressure

Hypertension ◽  
1999 ◽  
Vol 34 (1) ◽  
pp. 102-106 ◽  
Author(s):  
Mario J. Carvalho ◽  
Anton H. van den Meiracker ◽  
Frans Boomsma ◽  
Joao Freitas ◽  
Arie J. Man in ‘t Veld ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Sympathetic Nervous

Interactions between ANG II, sympathetic nervous system, and baroreceptor reflexes in regulation of blood pressure

1992 ◽  
Vol 262 (6) ◽  
pp. E763-E778 ◽  
Author(s):  
I. A. Reid
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Blood Pressure Control ◽  
Cardiovascular Responses ◽  
Pressure Control ◽  
Ang Ii ◽  
Arterial Blood ◽  
Baroreceptor Reflexes ◽  
Sympathetic Nervous

The renin-angiotensin system plays an important role in the regulation of arterial blood pressure and in the development of some forms of clinical and experimental hypertension. It is an important blood pressure control system in its own right but also interacts extensively with other blood pressure control systems, including the sympathetic nervous system and the baroreceptor reflexes. Angiotensin (ANG) II exerts several actions on the sympathetic nervous system. These include a central action to increase sympathetic outflow, stimulatory effects on sympathetic ganglia and the adrenal medulla, and actions at sympathetic nerve endings that serve to facilitate sympathetic neurotransmission. ANG II also interacts with baroreceptor reflexes. For example, it acts centrally to modulate the baroreflex control of heart rate, and this accounts for its ability to increase blood pressure without causing a reflex bradycardia. The physiological significance of these actions of ANG II is not fully understood. Most evidence indicates that the actions of ANG to enhance sympathetic activity do not contribute significantly to the pressor response to exogenous ANG II. On the other hand, there is considerable evidence that the actions of endogenous ANG II on the sympathetic nervous system enhance the cardiovascular responses elicited by activation of the sympathetic nervous system.

Abstract 291: Antihypertensive Effect Of Bia 5-1058 a New Selective Peripheral Dopamine β-hydroxylase Inhibitor

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Bruno Igreja ◽  
Nuno M Pires ◽  
Lyndon C Wright ◽  
Patrío Soares-da-Silva
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Receptor Antagonist ◽  
Antihypertensive Effect ◽  
Antihypertensive Drugs ◽  
Radio Telemetry ◽  
Sympathetic Nerves ◽  
Maximum Reduction ◽  
Sympathetic Nervous

The sympathetic nervous system can alter blood pressure by modulation of cardiac output, peripheral vascular resistance and renal function. One strategy for controlling sympathetic nerve function is to reduce the biosynthesis of norepinephrine (NE) via inhibition of dopamine β-hydroxylase (DβH; EC 1.14.17.1 ), the enzyme that catalyses the conversion of dopamine (DA) to NE in sympathetic nerves. BIA 5-1058 is a reversible DβH inhibitor that decreases NE levels in peripheral sympathetically innervated tissues slowing down sympathetic nervous system drive, without effect in brain tissues. In freely moving SHR implanted with radio-telemetry transmitters single administration of BIA 5-1058 showed a dose (3, 30 and 100 mg/Kg) and time dependent effect on blood pressure with no significant effect on heart rate (HR) and total activity monitored over a 96-hour period. The maximum reduction on systolic blood pressure (SBP) was -10.8, -21.1 and -35.2 mmHg for 3, 30 and 100 mg/Kg, respectively and the maximum reduction on diastolic blood pressure (DBP) was -9.9, -18.4 and -24.8 mmHg for 3, 30 and 100 mg/Kg, respectively. The antihypertensive effect of BIA 5-1058 (30 mg/Kg) was further evaluated in combination with efficacious doses of well-known antihypertensive drugs, like the ACE inhibitor captopril, the AT1 receptor antagonist losartan, the diuretic hydrochlorothiazide, beta-blocker metoprolol, the alpha-1 receptor antagonist prazosin, and the calcium channel blocker diltiazem. All drugs were administered orally (single dose) in a cross-over design and the effect was monitored for 72 hours. The combination of BIA 5-1058 with any of the tested antihypertensive drugs caused a stronger and prolonged blood pressure decrease than any of the compounds alone.In conclusion, peripheral DβH inhibitors can be used, alone or in combination with others antihypertensive drugs, to reduce blood pressure.

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