Epinephrine enhances neurogenic vasoconstriction in the rat perfused kidney.

Abstract

Epinephrine has been implicated in the genesis of some forms of hypertension. We have investigated the effects of epinephrine on vasoconstrictor responses evoked by adrenergic stimuli in the isolated perfused rat kidney. Low concentrations of epinephrine (2.5 - 5 X 10(-9) M) increased the amplitude of vasoconstrictor responses evoked by electrical stimulation of the renal adrenergic nerves. These concentrations of epinephrine had no effect on the basal perfusion pressure of the kidney or on the amplitude of vasoconstrictor responses evoked by exogenous norepinephrine. The potentiating effect of epinephrine persisted after infusion of the amine had ceased. Kidneys that had been perfused with 3H-epinephrine accumulated radioactivity, which could then be released by renal nerve stimulation. Cocaine (3 X 10(-5) M) reduced the renal accumulation of 3H-epinephrine and abolished both the persistent potentiating effect of the amine and the release of radioactivity evoked by subsequent nerve stimulation. The potentiating effect of epinephrine infusion was abolished by the beta 2-selective adrenergic receptor antagonist ICI 118,551 (3 X 10(-8) M), but not by the beta 1-selective adrenergic receptor antagonist atenolol (10(-6) M). These results indicate that concentrations of epinephrine that can be achieved during acute stress can enhance the amplitude of neurogenic vasoconstrictor responses. This effect appears to be mediated via a prejunctional beta 2-adrenergic receptor. The persistent nature of this effect may be due to the neuronal accumulation and subsequent release of epinephrine.

Epinephrine facilitates neurogenic vasoconstriction in humans.

“…30 min after the infusion of isoproterenol, which is not taken up by sympathetic nerves, the vasoconstrictor response to the reflex stimulus was not augmented, nor was the ratio of vasoconstrictor responses to LBNP/NE. Although there may be other differences between these two catecholamines that may affect local responses, these findings are consistent with previous observations, using catecholamine uptake blockers in isolated tissues (8) and humans (6). We propose that the amplification of neurogenic vasoconstriction seen after cessation of epinephrine infusion and not after isoproterenol is due to the neural uptake and subsequent release of epinephrine, causing a facilitation of NE release as was seen in period 2 sponse to NE during and post-EPI in series 1 were due to prior infusion ofthese alpha adrenoceptor agonists, a similar attenuation of the vasoconstrictor response to NE should have followed the prolonged infusion of NE in series 3.…”

“…We postulate that this is because offacilitated release of the transmitter. Although we did not study the effect of beta adrenoceptor antagonists on these responses, there is good evidence from experimental literature (4,7,8,12) and human studies (17) that the facilitated NE release seen during epinephrine infusions can be prevented by beta adrenoceptor blockade, and after epinephrine by beta adrenoceptor and catecholamine uptake blockade.…”

“…These receptors appear to be beta-2 in most species, including man (1)(2)(3)(4)(5)(6)(7)(8). Because the affinity of epinephrine for beta-2 receptors is more than 200-fold greater than that of NE, one of the physiological roles subserved by epinephrine may be to modulate NE release (2,9,10).…”

“…Epinephrine can be taken up into postganglionic sympathetic nerves and released as a co-transmitter with NE for 24 h after its uptake (8,(10)(11)(12)(13)(14). When released, epinephrine augments the simultaneous discharge of endogenous NE.…”

Rat renal epinephrine synthesis.

“…These receptors mediate renin release, renal vascular tone, and sodium reabsorption. E facilitates neuronal release of NE so it enhances vasoconstriction induced by the firing of renal sympathetic nerves (6). However, when a receptors are blocked, E increases renal blood flow by activating renal /2 receptors (7).…”