Role of the Renin Angiotensin System in Blood Pressure Allostasis-induced by Severe Food Restriction in Female Fischer rats

Abstract

Severe food restriction (FR) is associated with blood pressure (BP) and cardiovascular dysfunction. The renin-angiotensin system (RAS) regulates BP and its dysregulation contributes to impaired cardiovascular function. Female Fischer rats were maintained on a control (CT) or severe FR (40% of CT) diet for 14 days. In response to severe FR, BP allostasis was achieved by up-regulating circulating Ang-[1–8] by 1.3-fold through increased angiotensin converting enzyme (ACE) activity and by increasing the expression of AT1Rs 1.7-fold in mesenteric vessels. Activation of the RAS countered the depressor effect of the severe plasma volume reduction (≥30%). The RAS, however, still underperformed as evidenced by reduced pressor responses to Ang-[1–8] even though AT1Rs were still responsive to the depressor effects of an AT1R antagonist. The aldosterone (ALDO) response was also inadequate as no changes in plasma ALDO were observed after the large fall in plasma volume. These findings have implications for individuals who have experienced a period(s) of severe FR (e.g., anorexia nervosa, dieters, natural disasters) and suggests increased activity of the RAS in order to achieve allostasis contributes to the cardiovascular dysfunction associated with inadequate food intake.

Severe food restriction activates the central renin angiotensin system

“…These data indicate that sFR regulates MAP in part by activating the brain RAS. These findings extend our previous observation that administration of losartan into the bloodstream reduces MAP to a greater extent in sFR rats compared to the CT group (de Souza et al, ). The selective effect of central blockade of AT 1 Rs on MAP in sFR animals is similar to findings in the spontaneously hypertensive rat in a model of acute hemorrhage.…”

“…Before starting the 2 weeks sFR diet regimen, there were no differences between CT and sFR animal groups in initial BW [(g): CT, 201 ± 3 ( n = 22) vs. sFR, 207 ± 2 ( n = 24)]. Similarly to our previous findings (de Souza et al, ), 2 weeks of the sFR diet caused a 12% loss in final BW [(Final‐Initial (g)): CT, −0.1 ± 1.9 vs. sFR, −24.7 ± 1.7; p < .001]. Terminal measurements assessed by indwelling catheters showed the MAP was 9 mmHg lower (Figure a, inset ) and HR was 30 bpm lower (Figure d, inset ) in sFR rats when compared to animals fed a CT diet.…”

“…Increased AT 1 R binding in the PVN would increase sympathetic outflow and raise MAP (Dampney, ). Thus, the up‐regulation of AT 1 Rs in the PVN is a likely compensatory response to the depressor effects of hypovolemia‐induced by sFR (de Souza et al, ). This higher AT 1 R expression also could contribute to the previously observed increase in adrenergic response in the vasculature (de Souza et al, ) since it is known that AT 1 Rs located in the PVN can stimulate the sympathetic response (Dampney, ).…”

“…The concentration of protein in the homogenates were determined by the Pierce BCA protein assay kit (ThermoFischer). Ang‐[1‐8] metabolism was determined by liquid chromatography and tandem mass spectroscopy (LC‐MS/MS) as previously described (de Souza et al, ). In brief, tissue homogenates were spiked with Ang‐[1‐8] (100 ng/µg protein).…”

“…Animals lose approximately 15% of their normal BW over the 2 weeks period of sFR. Recently, we showed the RAS was activated in the periphery of female rats after 2 weeks on the sFR diet (de Souza et al, ). Plasma Ang‐[1‐8] was increased as well as the activity of angiotensin converting enzyme (ACE), which produces Ang‐[1‐8] from its inactive precursor Ang‐[1‐10].…”