Forskolin preferentially dilates the afferent arteriole in the canine kidney.

Abstract

ABSTRACT-Intrarenal infusion of forskolin (0.2,ug/kg/min) in anesthetized dogs increased renal blood flow (RBF) and glomerular filtration rate (GFR) to the same degree but did not change the mean arterial pressure or heart rate. Forskolin also increased urine flow and urinary sodium excretion. The proportional increases in RBF and GFR may result from a preferential action of forskolin to dilate the afferent arteriole.The role of adenosine 3'5'-cyclic monophosphate (cAMP) as a second messenger of hormone-or drug-induced vasodilation has been investigated. A rise in intracellular cAMP concentration is believed to be responsible for the relaxation of vascular smooth muscle by certain drugs. We previously reported that isoproterenol and glucagon, both stimulators of adenylate cyclase, increased not only renal blood flow (RBF) but also glomerular filtration rate (GFR) (1, 2). These results suggest that these renal vasodilators show preferential action for dilating the preglomerular arteriole over the postglomerular arteriole. On the other hand, intrarenal infusion of acetylcholine or bradykinin increase RBF but do not alter GFR (3, 4), indicating that acetylcholine and bradykinin dilate both arterioles equally. These findings suggest that the different responses of the afferent and efferent arterioles result from stimulation of a different adenylate cyclase-cAMP system in each arteriole.Forskolin is a powerful adenylate cyclase stimulator and a good pharmacological tool for investigating the role of cAMP in vasodilation (5). We have reported that forskolin stimulates the accumulation of cAMP in the isolated afferent arterioles (6). In the present study, we examined the effects of intrarenal infusion of forskolin on renal hemodynamics and renal function and discussed the role of cAMP on the regulation of renal hemodynamics.Experiments were performed on adult mongrel dogs of both sexes, weighing 9 -13 kg, which were maintained on standard laboratory diet for I week. The animals were anesthetized with sodium pentobarbital (30 mg/kg i.v.) and were given additional doses as required. After tracheotomy, the dogs were mechanically ventilated with room air. Catheters were inserted into the right brachial vein and artery for infusion of saline and for arterial blood sampling. Renal arterial pressure was measured from a catheter inserted into the right femoral artery and advanced into the abdominal aorta just below the left renal artery. The left kidney was exposed through a retroperitoneal flank incision. The kidney was denervated by carefully sectioning all visible nerve fibers associated with the renal vessels.

Effects Of NKH477 On Endothelin‐1‐Induced Renal Responses In Anaesthetized Dogs

“…Studies in the resistance vessels of the dog kidney have shown that ET‐1 contracts both afferent and efferent arterioles 10 and that forskolin stimulates the accumulation of cAMP in the isolated afferent arteriole and preferentially dilates the afferent arteriole. 11,12 However, FE Na during NKH477 infusion in the presence of ET‐1 was still lower than that in the absence of ET‐1. Therefore, NKH477 does not seem to inhibit the tubular action of ET‐1.…”

Plectranthus barbatus: A Review of Phytochemistry, Ethnobotanical Uses and Pharmacology – Part 2

“…The inhibitory effect of forskolin on the contractions of the uterine rings from rats at 16 days of gestation was found to involve the activation of adenylyl cyclase, the adenosine triphosphate-dependent potassium channels and, to a greater extent, calcium-dependent potassium channels [106]. Moreover, intrarenal infusion of forskolin in anesthetized dogs was reported to cause natriuresis with increasing renal blood flow and glomerular filtration rate, which is due to the ability of forskolin to preferentially dilate the afferent arterioles [107]. Eye: Topical ocular administration of 1% forskolin suspension in rabbits, monkeys and human volunteers, who were free from eye disease, was reported to lower the intraocular pressure as a result of a reduction of the net aqueous flow without significant change in outflow facility [108][109][110][111][112].…”