α‐Adrenergic regulation of human renal function

Summary— Pharmacological and molecular cloning techniques have identified six human subtypes of α‐adrenoceptors which are designated α 1A , α 1B , α 1D , α 2A , α 2B and α 2C . At the protein level human kidney expresses predominantly α 2A ‐adrenoceptors while other α 2 ‐adrenoceptor subtypes or α 1 ‐adrenoceptors have not been detected consistently in radioligand binding studies. However, the presynaptic receptors, which inhibit noradrenaline release in the human kidney, appear to belong to the α 2C ‐subtype. Intrarenal infusion of the nonselective α 1 ‐adrenoceptor antagonist, phentolamine, and of the selective α 2 ‐adrenoceptor antagonist, yohimbine, but not of the selective α 1 ‐adrenoceptor antagonist, doxazosin, increase renal blood flow and renin release in hypertensive patients undergoing diagnostic renal angiography. Thus, α 2 ‐ but not α 1 ‐adrenoceptors appear to mediate a tonic renal vasoconstriction and inhibition of renin release. Effects of systemically given α‐adrenoceptor agonists and antagonists are difficult to interpret on a mechanistic level since direct effects in the kidney and indirect effects due to baroreflex activation and peripheral presynaptic and central sympatholytic actions may at least partially offset each other. Moreover, some of these drugs may additionally act independent of α‐adrenoceptors, for example, via imidazoline recognition sits. The net result in a given subject may depend on the endogenous sympatho‐adrenal tone. Thus, for each target population of interest, effects have to be described empirically for each drug.