Enalapril Attenuates the Exaggerated Sympathetic Response to Physical Stress in Prenatally Programmed Hypertensive Rats

Abstract

Adulthood hypertension can be prenatally programmed by maternal dietary protein deprivation. We have shown that the sympathetically-mediated pressor response to physical stress is exaggerated in prenatally programmed hypertensive rats (PPH). The mechanisms underlying this abnormal responsiveness remain undetermined. The renin-angiotensin system is known to effect sympathetic nerve activity. Therefore, the purpose of this study was to determine whether inhibition of the renin-angiotensin system attenuates the enhanced sympathetic and pressor responses to physical stress in PPH. Changes in renal sympathetic nerve activity and blood pressure in response to i) hindlimb contraction; ii) hindlimb stretch; and iii) hindlimb intra-arterial capsaicin administration were assessed in control and PPH rats chronically treated (from age 3 wks) with either vehicle or the angiotensin-converting enzyme inhibitor enalapril. Conscious resting systolic arterial pressure was significantly greater in PPH (142±5 mmHg) than control (128±2 mmHg) after vehicle treatment (P<0.05). Resting systolic pressure was reduced by enalapril treatment in PPH (125±2mmHg) but had no effect in control (128±2 mmHg). The pressor and renal sympathetic responses to muscle contraction and stretch were significantly higher in decerebrate PPH than decerebrate control in vehicle treated groups. Responses to capsaicin were variable. Enalapril significantly attenuated the enhanced contraction-induced elevations in mean pressure (vehicle=45±6 mmHg; enalapril=21±3 mmHg) and renal sympathetic activity (vehicle=175±22%; enalapril=89±23%) in PPH. Its effects were similar on responses to stretch in PPH but were equivocal during capsaicin administration. The results suggest that the renin-angiotensin system contributes to the enhancement of the renal sympathetic and pressor responses to physical stress in PPH.

Dynamic exercise training prevents exercise pressor reflex overactivity in spontaneously hypertensive rats

“…This characteristic EPR overactivity has been shown to manifest not only in SHR but also in other models of the disease such as prenatally programmed hypertension (41,44) and angiotensin II-induced hypertension (24). In SHR, 3 mo of voluntary wheel running attenuated the cardiovascular and sympathetic responses to EPR activation.…”

Exercise training improves functional sympatholysis in spontaneously hypertensive rats through a nitric oxide-dependent mechanism

“…Additionally, the sympathetically mediated blood pressure response to exercise is also abnormally elevated in hypertensive animals (32,(41)(42)(43)(44)52) and patients (11,12,36,58). The impairments in functional sympatholysis might be a mechanism by which the blood pressure response to physical exercise is exaggerated in this disease.…”

Mechanisms involved in developmental programming of hypertension and renal diseases. Gender differences

“…Finally, it has been proposed that RAS may also be involved in the enhanced renal sympathetic activity ( Figure 5). This latter possibility is supported by studies showing that hypertension is associated to an enhanced AT 1 receptor expression in several areas of the brain and that the intracerebroventricular administration of an ARA induces a significant reduction in BP [120]. It has also been reported that the administration of a CEI prevents the exaggerated renal sympathetic and pressor responses to physical stress in rats with developmental programming of hypertension [121].…”