Renal effects of the antihypertensive, guanabenz, in the dog
Strandhoy, J.W.; Morris, M.; Buckalew, V.M.
Journal of Pharmacology and Experimental Therapeutics 221(2): 347-352
1982
ISSN/ISBN: 0022-3565 PMID: 7077529 Document Number: 192870
Clonidine and guanabenz produce a water diuresis attributed to decreased antidiuretic hormone (ADH) release or renal antagonism of salt and water reabsorption. The effects of guanabenz were examined in pentobarbital-anesthetized dogs. Guanabenz (1 .mu.g/kg per min i.v.) significantly increased glomerular filtration rate, urine flow and Na excretion and reduced heart rate and blood pressure. Renal blood flow was unchanged. Associated with a fall in urine osmolality of 977 mOsmol/kg of H2O (P < 0.001), plasma ADH concentration fell from 7.92 to 5.23 pg/ml (P < 0.01). Several interventions were examined to modify the renal and cardiovascular actions of guanabenz. Renal denervation or antihistamines did not change its effects. Indomethacin raised urine osmolality in spite of a decrease in ADH to 2.38 pg/ml. Guanabenz decreased urine osmolality from 2109 to 448 mOsmol/kg of H2O (P < 0.001) and significantly increased salt and water excretion without a further decrease in ADH. This implicates a renal excretory change not attributable to decreased ADH secretion or increased renal prostaglandin synthesis. Yohimbine, an .alpha.-2 antagonist, prevented the change in heart rate and ADH secretion caused by guanabenz and significantly reduced its diuretic effect. Prazosin, an .alpha.-1 antagonist, attenuated the bradycardia but did not affect the diuresis or the decrease in ADH secretion caused by guanabenz. Neither antagonist reduced the guanabenz-induced natriuresis nor the decrease in blood pressure. The increase in glomerular filtration rate produced by guanabenz was partially reduced by prazosin and enhanced by yohimbine. The diuretic and natriuretic effects of guanabenz evidently involve decreased ADH secretion and decreased tubular reabsorption of salt and water. The diuretic effect depends upon stimulation of .alpha.-2 receptors, whereas neither the increase in glomerular filtration rate nor the increase in Na excretion produced by guanabenz are prevented by .alpha.-2 adrenergic blockade.