Effects of [Sar1, Ile8]-angiotensin II on rostral ventrolateral medulla neurons and blood pressure in spontaneously hypertensive rats

Abstract

The present study was an attempt to determine the influence of brain angiotensin II, the activity of which is known to be higher in spontaneously hypertensive rat, on the spontaneous activity of the cardiovascular neurons in the rostral ventrolateral medulla of the spontaneously hypertensive rat. Both the spontaneous activity of the spinal projecting rostral ventrolateral medulla cardiovascular neurons and the arterial blood pressure were simultaneously measured in the pentobarbital-anesthetized spontaneously hypertensive rat and its normotensive control, the Wistar Kyoto rat, following microinjection to rostral ventrolateral medulla of an angiotensin II antagonist, [Sar1, Ile8]-angiotensin II (sarile). A microinjection method was developed that enabled us to perform extracellular recording of the rostral ventrolateral medulla cardiovascular neuron during the microinjection of drug to the vicinity of the neuron. It was found that sarile reduced both the arterial blood pressure and firing rate of some rostral ventrolateral medulla cardiovascular neurons dose-dependently. The effects of sarile were significantly greater in spontaneously hypertensive rat than in the Wistar Kyoto rat. The present findings indicate that the rostral ventrolateral medulla cardiovascular neurons of spontaneously hypertensive rat exhibit an augmented sensitivity to endogenous brain angiotensin II. Such an increase in sensitivity to brain angiotensin II in the spontaneously hypertensive rat may contribute to the enhanced spontaneous activities of rostral ventrolateral medulla cardiovascular neurons, as in the sarile responsive single discharge units, even in the resting or prestimulation state. This interaction of brain angiotensin II and rostral ventrolateral medulla cardiovascular neurons is likely to be contributory to the genesis of hypertension in this strain of rats.