Endogenous adenosine restrains renin release in conscious rats.

Abstract

The purpose of this study was to test the hypothesis that endogenous adenosine functions to restrain the renin release response to pharmacological and pathophysiological stimuli. To achieve this objective, we examined the effects of an adenosine receptor antagonist, 1,3-dipropyl-8-(p-sulfophenyl)xanthine (DPSPX), on the renin release response induced by acute administration of hydralazine or by chronic clipping of the left renal artery (renovascular hypertensive rats). In conscious, unrestrained rats, DPSPX significantly increased plasma renin activity (PRA) in control rats, in rats treated with hydralazine, and in renovascular hypertensive rats. The effect of DPSPX on PRA was significantly greater in rats treated with hydralazine or in renovascular hypertensive rats compared with control rats. DPSPX did not influence arterial blood pressure in any group, did not affect the measurement of PRA, and did not alter the elimination of renin activity from the circulation. Additional experiments were performed in the in situ autoperfused kidney so that the effects of DPSPX on renal hemodynamics and renal excretory function could be assessed. In this experimental model, DPSPX also increased PRA in hydralazine-treated rats and in renovascular hypertensive rats without affecting arterial pressure, renal blood flow, or sodium excretion. In a final set of studies in conscious, unrestrained rats, adenosine deaminase increased PRA in a dose-dependent manner in hydralazine-treated rats and significantly increased the slope of the relation between PRA and the depressor response to hydralazine. We conclude: 1) Although the kidney has both A1 and A2 adenosine receptors mediating inhibitory and stimulatory actions, respectively, on renin release, the dominant effect of endogenous adenosine on renin release is inhibitory. 2) Even under basal physiological conditions, endogenous adenosine tonically inhibits renin release. 3) This inhibitory effect is augmented whenever the renin-angiotensin system is stimulated regardless of the approach used to activate renin release. 4) Endogenous adenosine negatively modulates renin release by a direct effect on juxtaglomerular cells.

Modulatory effects of endogenous adenosine on epinephrine secretion from the adrenal medulla of the rat.

“…These blood pressure data were obtained before the baseline epinephrine and norepinephrine samples were withdrawn and before epinephrine and norepinephrine samples were withdrawn at 60 minutes after hydralazine. As published previously, 14 the depressor effect of hydralazine remained at the same level during the entire experimental period.…”

“…This result indicates that the inhibitory effect of endogenous adenosine on epinephrine release from the adrenal medulla and its suppressing effect on plasma norepinephrine levels were at least partially through the modulation of the RAS. Based on our prior published data, 14 - 20 we suggest that the effect of adenosine on RAS is through the inhibitory effect of endogenous adenosine on renin release. DP-SPX, an adenosine antagonist, causes an increase in renin level, which leads to a higher angiotensin II level.…”

“…Regarding the interaction between adenosine receptors and the RAS, previous studies have showed that the inhibitory effect of adenosine on the RAS is augmented when the RAS is activated, eg, during sodium restriction, 20 during hydralazine-induced hypotension, in twokidney, one clip renovascular hypertensive rats, 14 and during hemorrhagic shock. 21 There is also evidence that angiotensin II enhances norepinephrine release from mouse atria, 22 cultured adrenal medulla cells, 23 and postganglionic nerve endings.…”

“…14 Briefly, the day before the scheduled experiment, male Sprague-Dawley rats (National Defense Medical Center, Taipei, Taiwan) were anesthetized with pentobarbital sodium (Sigma Chemical Co, 30 mg/kg IP). Both the left carotid artery and left jugular vein were cannulated with a PE-50 catheter (Clay Adams).…”

Coffee, caffeine and blood pressure: a critical review

“…Plasma renin activity was increased, which could have caused the renal vasoconstriction via increased angiotensin II concentrations. Acutely administered caffeine increased plasma renin activity in experimental animals (Ohnishi et al, 1987) and in man (Robertson et al, 1978(Robertson et al, , 1981, probably through the antagonism of adenosine receptors on juxtaglomerular cells (Kuan et al, 1990). In some studies, however, no signi®cant effect of acute caffeine intake on plasma renin activity was observed (Passmore et al, 1987;Nussberger et al, 1990), or else the increase was attenuated after chronic administration of caffeine (Robertson et al, 1981(Robertson et al, , 1984Eggertsen et al, 1993).…”