Increased activity of the renin-angiotensin and sympathetic nervous systems is required for regulation of the blood pressure in rats fed a low-protein diet

Exp Physiol. 2013 Jan;98(1):57-66. doi: 10.1113/expphysiol.2012.066712. Epub 2012 Jun 22.

Abstract

Previous studies have shown that postweaning protein restriction induces changes in the sympathetic nervous system in rats, leading to alterations in cardiovascular parameters. In addition, the renin-angiotensin system is also affected in these animals. Here, we hypothesized that adjustments in the interaction between the RAS and SNS underlie the cardiovascular adaptations observed in rats fed a low-protein diet. Thus, we evaluated the alterations in the mean arterial pressure (MAP) and heart rate of Fisher rats fed a protein-deficient diet before and after systemic administration of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II (Ang II) type 1 (AT(1)) receptor antagonist losartan alone or in combination with the α(1)-adrenergic receptor antagonist prazosin. Administration of enalapril or losartan decreased the MAP only of rats under protein restriction. Prazosin injection after the infusion of losartan caused a further decrease in the MAP of malnourished rats. In contrast, only the administration of prazosin elicited a reduction in the MAP of control animals. When the sequence of administration of the antagonists was inverted, infusion of prazosin in animals fed the standard or the low-protein diet induced a reduction in the MAP that was further decreased by the subsequent injection of losartan. Importantly, in both protocols the responses of malnourished animals to losartan were markedly greater when compared with the control group. Moreover, these animals presented lower levels of circulating Ang II and a reduced responsiveness to Ang II. In contrast, the expression of AT(1) receptors in the aorta of malnourished animals was increased. Thus, our data suggest that the renin-angiotensin system is an important factor supporting blood pressure in rats fed a low-protein diet and that the sympathetic nervous system activity in these animals is under strong influence of Ang II acting via AT(1) receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism*
  • Angiotensin Receptor Antagonists / pharmacology
  • Animals
  • Arterial Pressure / drug effects*
  • Diet, Protein-Restricted
  • Enalapril / pharmacology
  • Heart Rate / drug effects
  • Losartan / pharmacology
  • Male
  • Prazosin / pharmacology
  • Rats
  • Rats, Inbred F344
  • Receptor, Angiotensin, Type 1 / drug effects
  • Receptor, Angiotensin, Type 1 / metabolism*
  • Renin-Angiotensin System / physiology
  • Sympathetic Nervous System / physiology

Substances

  • Angiotensin Receptor Antagonists
  • Receptor, Angiotensin, Type 1
  • Angiotensin II
  • Enalapril
  • Losartan
  • Prazosin