Published Online
on September 9, 2002

A more recent version of this article appeared on October 1, 2002

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Submitted on June 11, 2002
Revised on July 8, 2002

Ventrolateral Medulla AT₁ Receptors Support Blood Pressure in Hypertensive Rats

Satoru Ito; Kazutoshi Komatsu; Kazuyoshi Tsukamoto; Katsuo Kanmatsuse; and Alan F. Sved^*

From the Second Department of Internal Medicine, Nihon University School of Medicine (S.I., K. Komatsu, K.T., K. Kanmatsuse), Tokyo, Japan; and the Department of Neuroscience, University of Pittsburgh (A.F.S.), Pittsburgh, Pa.

^* To whom correspondence should be addressed. E-mail: sved{at}pitt.edu.

Abstract—Angiotensin within the central nervous system appears to be important for the maintenance of hypertension in spontaneously hypertensive rats. This study addresses the hypothesis that blockade of AT₁ receptors in the rostral ventrolateral medulla would decrease blood pressure in spontaneously hypertensive rats and that this tonically active AT₁-mediated input to the rostral ventrolateral medulla arises from the hypothalamic paraventricular nucleus. Injection of the nonpeptide AT₁ receptor antagonist valsartan bilaterally into the rostral ventrolateral medulla of choralose-anesthetized adult spontaneously hypertensive rats produced a dose-related decrease in mean arterial pressure, with a maximal effect of 30 mm Hg. Inhibition of the paraventricular nucleus by local injection of muscimol elicited a similar response, which was inhibited by prior injection of valsartan into the rostral ventrolateral medulla. In contrast, in control Wistar-Kyoto rats, neither valsartan injected into the rostral ventrolateral medulla nor muscimol injected into the paraventricular nucleus had a substantial effect on arterial pressure. These data indicate that in spontaneously hypertensive rats but not in Wistar-Kyoto rats, rostral ventrolateral medulla vasomotor neurons are tonically excited by endogenous stimulation of AT₁ receptors, and this input is apparently driven from the hypothalamus. These results suggest that the rostral ventrolateral medulla is one site that the brain renin-angiotensin system acts to maintain elevated blood pressure in spontaneously hypertensive rats.

Key words: brain • receptors, angiotensin • central nervous system • hypertension, experimental • hypothalamus • angiotensin

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