Water Diuresis from Clonidine (Catapres)

Abstract

Available clinical and experimental evidence indicates that clonidine 2-2(2,6-di-ch1orophenylamino)-2 imidazoline hydrochloride, has potent hypotensive, bradycardic and bradypneic properties (1-6). It also produces sedation and local anesthesia, inhibits gastric acid secretion, and raises blood sugar (7). Its effect on blood pressure in the anesthetized dog is a bimodal one. An initial short rise is followed by a prolonged decrease. Similar observations have been reported in the rabbit, rat, and cat (8,9). Concerning the actions of clonidine upon renal hemodynamic and excretory functions, it was shown by Onesti et al. (6) that when the drug was given either orally or intravenously to dogs and man, it had no effect on the effective renal plasma flow, glomerular filtration rate, and potassium excretion, while it decreased the excretion of sodium and chloride. The pathophysiologic mechanism by which clonidine exerts its renal effects has not as yet been elucidated. The purpose of this study, therefore, was to attempt to clarify if clonidine has any direct renal effect by infusing the drug in small amounts into the renal artery of one kidney of the anesthetized dog and comparing its effects against the other kidney without disturbing systemic hemodynamics. In a second group of animals the drug was given intravenously in order to study the systemic effects and significance of a different route of administration.Materials and methods. Sixteen well-conditioned dogs of both sexes weighing 22-25 kg were used in this study. The animals were anesthetized with sodium pentobarbital (30 mg/kg) and kept lightly anesthetized for the whole length of the experiments. All the animals were intubated and ventilated with room air. The jugular vein and the external carotid artery were exposed and catheterized with polyethylene tubing for con-tinuous infusion and monitoring of the blood pressure, respectively. The dogs were primed with a solution containing inulin and paraaminohippuric acid (PAH) in isosmotic saline. Thereafter the dogs were maintained with a sustaining solution of similar composition but different concentration administered at a rate of 6.0 ml/min, in order to maintain the dog's blood levels of inulin and PAH at 25-30 mg% and 2-4 mg%, respectively.A mercury manometer was connected to the external carotid artery for continuous monitoring of the blood pressure and blood sampling from a manifold. Both ureters were exposed through a midline incision and catheterized with polyethylene tubing for continuous urine collection into graduated cylinders. In 10 dogs (Group 1) the right renal artery was exposed through a left flank incision and cannulated through the abdominal aorta with an 18-gauge Rochester needle for infusion of the drug. In six dogs (Group 2) the drug was given intravenously. The experiments in both groups were divided into a control and experimental period. The control period consisted of four urine collections 20 min each and the experimental period of six collections 20 min each also. Blood for clearances of...

Renal effects of infusion of rilmenidine and guanabenz in conscious dogs: contribution of peripheral and central nervous system α2–adrenoceptors

“…In previous studies in dogs (either conscious or anaesthetized), the effects on sodium excretion of intravascular (either intravenous or intrarenal) administration of x2adrenoceptor agonists such as clonidine and guanabenz have ranged from antinatriuresis to natriuresis. However, these studies are difficult to interpret since in all except one (Strandhoy et al, 1983) no control experiments are reported (Marchand et al, 1971;Chrysanthakopoulos & Lavender, 1975;Olsen, 1976;Strandhoy et al, 1982). Our study clearly shows that intravenous administration of guanabenz, which is an a2-adrenoceptor agonist with very low affinity for 1,-binding sites, causes a diuresis but not a natriuresis in conscious normally-hydrated dogs, regardless of whether their autonomic reflexes are intact, or blocked by administration of pentolinium.…”

Abbott‐57219[SCH‐40054]: A Novel Nasal Decongestant

“…The compound produced highly significant increases in the excretion of water and sodium and chloride ions, whereas the potassium excretion remained unaffected. This effect was highly reminiscent of that produced by clonidine (4) and suggestive of a lack of correlation with the compound's adrenergic receptor selectivity in anesthetized dogs. Abbott-572 19 given intravenously at doses of I to 30 pg/kg exhibited hemodynamic effects consistent with its a-adrenoceptor agonistic profile: an increase in blood pressure and a decrease in heart rate, dP/ dt,,,, and cardiac output.…”

Is the Sympathetic System Detrimental in the Setting of Septic Shock, with Antihypertensive Agents as a Counterintuitive Approach? A Clinical Proposition

“…(2) Pharmacology [ 66 ]: Clonidine evokes increased free water clearance and urine flow in anesthetized dogs [ 282 ] and water and sodium diuresis (anti-antidiuretic hormone: ADH [ 283 , 284 , 285 ]), a large increase in urine output and the anti-inflammatory cytokine IL-10, and a lowering of the pro-inflammatory cytokine IL-6 in septic sheep [ 197 ] without changes in creatinine clearance or sodium excretion. Low dose clonidine (0.25 μg·kg −1 ·h −1 ) elicited vasodilation and increased CO (presumably increased SV) [ 197 ], a lowering of plasma renin activity, and sodium and weight loss [ 286 ] in hypertensive patients.…”