Effects of alpha-2 agonists on renal function in hypertensive humans.
Centrally acting adrenergic agonists, by decreasing peripheral adrenergic activity, are effective antihypertensive agents. The older agents, however, especially methyldopa, have been associated with weight gain, clinical edema, and antihypertensive tolerance when used as monotherapy. While acute studies in humans have demonstrated weight gain and sodium retention with clonidine and guanabenz, chronic administration results in a decrease in weight and plasma volume. The absence of chronic weight gain and of sodium retention could be the result of a counterbalance between hypotension-related antinatriuresis, secondary to a decrease in glomerular filtration rate and renal blood flow, and natriuretic activity, as a result of a decrease in renal sympathetic tone. Whereas natriuresis and water diuresis have been demonstrated in animals with acute clonidine or guanabenz administration, this has not been demonstrated in humans. Recent studies in which saline administration was used to precondition humans to a subsequent natriuretic stimulus (i.e., guanabenz-induced decreased renal adrenergic activity) resulted in stabilization of renal blood flow and natriuresis. Selective reduction renal sympathetic activity affecting salt and water transport may explain why guanabenz and probably also clonidine seem to be devoid of the sodium/fluid-retaining properties that are common with other antihypertensive agents. Because agents of this class have effects other than pure central alpha-2 agonism (such as alpha-1 activity), they might have confounding and counterbalancing side effects leading to sodium and water retention.
Goldberg
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Gehr
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D005919:Glomerular Filtration Rate; D006143:Guanabenz / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects*; D008750:Methyldopa / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D008750:Methyldopa; D006143:Guanabenz; D003000:Clonidine