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(Hypertension. 2000;36:417.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Contribution of Angiotensin-(1–7) to Blood Pressure Regulation in Salt-Depleted Hypertensive Rats

Shridhar N. Iyer; David B. Averill; Mark C. Chappell; Kazuo Yamada; Alicia J. Allred; Carlos M. Ferrario

From The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC.

Correspondence to Carlos M. Ferrario, MD, The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157. E-mail cferrari{at}wfubmc.edu

Abstract—We exposed 63 adult spontaneously hypertensive rats (SHR) and 10 (mRen-2)27 transgenic hypertensive rats to a 12-day regimen of either a normal diet (0.5%) or a low-salt diet (0.05%) to evaluate the hypothesis that the vasodepressor heptapeptide, angiotensin-(1–7) [Ang-(1–7)], buffers the pressor effects of angiotensin II during endogenous stimulation of the renin-angiotensin system. Catheters were inserted into a carotid artery and jugular vein under light anesthesia the day before the experiment. Separate groups of conscious instrumented SHR were given short-term infusions of an affinity-purified monoclonal Ang-(1–7) antibody or the neprilysin inhibitor SCH 39370. In addition, SHR and (mRen-2)27 rats were given the Ang-(1–7) receptor antagonist [D-Ala⁷]Ang-(1–7). Exposure to the low-salt diet increased plasma renin activity and elevated plasma levels of angiotensin I and angiotensin II in SHR by 81% and 68%, respectively, above values determined in SHR fed a normal salt diet. Concentrations of angiotensin I and angiotensin II were also higher in the kidney of salt-depleted SHR, whereas plasma and renal tissue levels of Ang-(1–7) were unchanged. Infusion of the Ang-(1–7) antibody produced dose-dependent pressor and tachycardic responses in salt-depleted SHR but no effect in SHR maintained on a normal-salt diet. A comparable cardiovascular response was produced in salt-depleted SHR given either SCH 39370 or [D-Ala⁷]Ang-(1–7). These agents had negligible effects on SHR fed a normal-salt diet. Blockade of Ang-(1–7) receptors produced a similar cardiovascular response in (mRen-2)27 transgenic hypertensive rats fed a low-salt diet. Injections of the heat-inactivated antibody or the subsequent infusion of the antibody to rats given [D-Ala⁷]Ang-(1–7) produced no additional effects. The data support the hypothesis that the hemodynamic effects of neurohormonal activation after salt restriction stimulate a tonic depressor action of Ang-(1–7).

Key Words: angiotensin II • blood pressure • hypertension, experimental • receptors, angiotensin • renin

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