scholarly journals Sex-specific computational models for blood pressure regulation in the rat

2020 ◽  
Vol 318 (4) ◽  
pp. F888-F900
Author(s):  
Sameed Ahmed ◽  
Anita T. Layton
Keyword(s):  
Blood Pressure ◽  
Computational Models ◽  
Sympathetic Nerve Activity ◽  
Blood Pressure Regulation ◽  
Female Rats ◽  
Pressure Regulation ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Sodium Handling ◽  
Renal Sympathetic

In the past decades, substantial effort has been devoted to the development of computational models of the cardiovascular system. Some of these models simulate blood pressure regulation in humans and include components of the circulatory, renal, and neurohormonal systems. Although such human models are intended to have clinical value in that they can be used to assess the effects and reveal mechanisms of hypertensive therapeutic treatments, rodent models would be more useful in assisting the interpretation of animal experiments. Also, despite well-known sexual dimorphism in blood pressure regulation, almost all published models are gender neutral. Given these observations, the goal of this project is to develop the first computational models of blood pressure regulation for male and female rats. The resulting sex-specific models represent the interplay among cardiovascular function, renal hemodynamics, and kidney function in the rat; they also include the actions of the renal sympathetic nerve activity and the renin-angiotensin-aldosterone system as well as physiological sex differences. We explore mechanisms responsible for blood pressure and renal autoregulation and notable sexual dimorphism. Model simulations suggest that fluid and sodium handling in the kidney of female rats, which differs significantly from males, may contribute to their observed lower salt sensitivity as compared with males. Additionally, model simulations highlight sodium handling in the kidney and renal sympathetic nerve activity sensitivity as key players in the increased resistance of females to angiotensin II-induced hypertension as compared with males.

scholarly journals Role of the heart in blood pressure lowering during chronic baroreflex activation: insight from an in silico analysis

2018 ◽  
Vol 315 (5) ◽  
pp. H1368-H1382 ◽  
Author(s):  
John S. Clemmer ◽  
W. Andrew Pruett ◽  
Robert L. Hester ◽  
Radu Iliescu ◽  
Thomas E. Lohmeier
Keyword(s):  
Blood Pressure ◽  
Mathematical Model ◽  
Renal Denervation ◽  
Sympathetic Nerve Activity ◽  
Blood Pressure Lowering ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Pressure Lowering ◽  
Renal Sympathetic ◽  
Stimulation Of

Electrical stimulation of the baroreflex chronically suppresses sympathetic activity and arterial pressure and is currently being evaluated for the treatment of resistant hypertension. The antihypertensive effects of baroreflex activation are often attributed to renal sympathoinhibition. However, baroreflex activation also decreases heart rate, and robust blood pressure lowering occurs even after renal denervation. Because controlling renal sympathetic nerve activity (RSNA) and cardiac autonomic activity cannot be achieved experimentally, we used an established mathematical model of human physiology (HumMod) to provide mechanistic insights into their relative and combined contributions to the cardiovascular responses during baroreflex activation. Three-week responses to baroreflex activation closely mimicked experimental observations in dogs including decreases in blood pressure, heart rate, and plasma norepinephrine and increases in plasma atrial natriuretic peptide (ANP), providing validation of the model. Simulations showed that baroreflex-induced alterations in cardiac sympathetic and parasympathetic activity lead to a sustained depression of cardiac function and increased secretion of ANP. Increased ANP and suppression of RSNA both enhanced renal excretory function and accounted for most of the chronic blood pressure lowering during baroreflex activation. However, when suppression of RSNA was blocked, the blood pressure response to baroreflex activation was not appreciably impaired due to inordinate fluid accumulation and further increases in atrial pressure and ANP secretion. These simulations provide a mechanistic understanding of experimental and clinical observations showing that baroreflex activation effectively lowers blood pressure in subjects with previous renal denervation. NEW & NOTEWORTHY Both experimental and clinical studies have shown that the presence of renal nerves is not an obligate requirement for sustained reductions in blood pressure during chronic electrical stimulation of the carotid baroreflex. Simulations using HumMod, a mathematical model of integrative human physiology, indicated that both increased secretion of atrial natriuretic peptide and suppressed renal sympathetic nerve activity play key roles in mediating long-term reductions in blood pressure during chronic baroreflex activation.

Interactions between ANP and ANG II in regulating blood pressure and sympathetic outflow

1991 ◽  
Vol 260 (6) ◽  
pp. R1145-R1151 ◽  
Author(s):  
M. K. Steele ◽  
D. G. Gardner ◽  
P. L. Xie ◽  
H. D. Schultz
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve Activity ◽  
Ang Ii ◽  
Contrast Injection ◽  
Synthesis Inhibitor ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Arterial Blood ◽  
Pressor Responses ◽  
Renal Sympathetic

In anesthetized rats with sinoaortic denervation, intracerebroventricular (icv) injection of atrial natriuretic peptide (ANP) resulted in decreased mean arterial blood pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) (depressor effects), whereas icv angiotensin II (ANG II) produced increases in these variables (pressor effects). The depressor effects of ANP were slower in onset and longer in duration than the pressor effects of ANG II. Intracerebroventricular injection of the ANG II-receptor blocker sarthran or the ANG II-synthesis inhibitor captopril resulted in a significant reduction in MAP; HR and RSNA were not affected. Both sarthran and captopril abolished the depressor responses to icv ANP. In contrast, injection of an anti-rat ANP antibody, which blocked the depressor effects of icv ANP, did not by itself modify MAP, HR, or RSNA, nor did the antibody affect the pressor responses to icv ANG II. These data suggest that, in this animal model, the depressor effects of icv ANP are mediated by the inhibition of brain ANG II-dependent neural activity. These results also demonstrate that, in this preparation, the endogenous ANG II system actively contributes to the maintenance of basal MAP, whereas the central ANP system, at least in regions accessible to the antirat ANP antibody, plays little role in this maintenance.

Central sympathoinhibition and peripheral neuronal uptake blockade after desipramine in rabbits

1991 ◽  
Vol 260 (4) ◽  
pp. R824-R832 ◽  
Author(s):  
G. Eisenhofer ◽  
T. Saigusa ◽  
M. D. Esler ◽  
H. S. Cox ◽  
J. A. Angus ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve Activity ◽  
Sympathetic Nerves ◽  
Neuronal Uptake ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Mediated Effects ◽  
Before And After ◽  
Peripheral Effect ◽  
Renal Sympathetic

Peripheral- and central nervous system (CNS)-mediated effects of desipramine (Des) on sympathetic nerves and the contribution of alpha 2-adrenoceptors to these effects were studied in conscious rabbits. Blood pressure, renal sympathetic nerve activity (SNA), and norepinephrine (NE) reuptake and spillover into plasma were measured before and after intracisternal (ic) or intravenous (i.v.) administration of Des. In other animals, NE spillover responses to i.v. Des were examined before and after alpha 2-adrenoceptor blockade with i.v. idazoxan. Treatment with i.v. Des blocked neuronal reuptake and decreased renal SNA but did not alter blood pressure or NE spillover. Decreased NE release by sympathetic nerves after i.v. Des was reflected by a decrease in the combined rate of NE reuptake and spillover. Treatment with ic Des (at 1.7% of the i.v. dose) decreased blood pressure and renal SNA and produced equivalent falls in NE reuptake and spillover, indicating little peripheral effect of centrally administered Des on the efficiency of neuronal reuptake. Thus Des had two distinct actions: the drug blocked neuronal reuptake by direct actions on nerve endings and reduced SNA by actions within the CNS. After ic Des, decreased SNA produced parallel falls in NE reuptake, spillover, and blood pressure. After i.v. Des, blockade of neurotransmitter reuptake increased NE concentrations at sympathoeffector junctions offsetting the fall in SNA, so that there was little change in NE spillover or blood pressure. However, after alpha 2-adrenoceptor blockade with i.v. idazoxan, NE spillover increased in response to i.v. Des. Thus the Des-induced decrease in NE release was partly mediated by an action of raised intrasynaptic NE concentrations on inhibitory alpha 2-adrenoceptors.

Increased renal sympathetic nerve activity leads to hypertension and renal dysfunction in offspring from diabetic mothers

2013 ◽  
Vol 304 (2) ◽  
pp. F189-F197 ◽  
Author(s):  
Aline Fernanda de Almeida Chaves Rodrigues ◽  
Ingrid Lauren Brites de Lima ◽  
Cássia Toledo Bergamaschi ◽  
Ruy Ribeiro Campos ◽  
Aparecida Emiko Hirata ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Renal Dysfunction ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Renal Nerves ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Diabetic Mothers ◽  
Renal Sympathetic

The exposure of the fetus to a hyperglycemic environment promotes the development of hypertension and renal dysfunction in the offspring at adult age. We evaluated the role of renal nerves in the hypertension and renal changes seen in offspring of diabetic rats. Diabetes was induced in female Wistar rats (streptozotocin, 60 mg/kg ip) before mating. Male offspring from control and diabetic dams were studied at an age of 3 mo. Systolic blood pressure measured by tail cuff was increased in offspring of diabetic dams (146 ± 1.6 mmHg, n = 19, compared with 117 ± 1.4 mmHg, n = 18, in controls). Renal function, baseline renal sympathetic nerve activity (rSNA), and arterial baroreceptor control of rSNA were analyzed in anesthetized animals. Glomerular filtration rate, fractional sodium excretion, and urine flow were significantly reduced in offspring of diabetic dams. Two weeks after renal denervation, blood pressure and renal function in offspring from diabetic dams were similar to control, suggesting that renal nerves contribute to sodium retention in offspring from diabetic dams. Moreover, basal rSNA was increased in offspring from diabetic dams, and baroreceptor control of rSNA was impaired, with blunted responses to infusion of nitroprusside and phenylephrine. Thus, data from this study indicate that in offspring from diabetic mothers, renal nerves have a clear role in the etiology of hypertension; however, other factors may also contribute to this condition.

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