Histamine H1 receptor antagonists inhibit autoregulation of renal blood flow in the dog

Academic Article

Abstract

  • Histamine H and H receptors are present in the canine renal circulation. We have examined the effects of H and H receptor antagonists on autoregulation of renal blood flow in the dog. Renal arterial pressure was reduced in a step-wise fashion to 80 mm Hg by means of an adjustable aortic clamp positioned above the left renal artery. Infusion of H antagonists, cimetidine or ranidine, into the left renal artery at 10 mol/min had no effect on autoregulation of renal blood flow or on the reactive hyperemia that occurred when the aortic constriction was released. By contrast, intrarenal infusion of 10 mol/min chlorpheniramine, an H receptor antagonist, reversibly attenuated reactive hypermia and the ability of the kidney to autoregulate renal blood flow. Similar results were obtained with other, chemically dissimilar H antagonists (terfenadine, diphenhydramine, and pyrilamine). The effects of chlorpheniramine on autoregulation of glomerular filtration rate also were evaluated. Before chlorpheniramine was infused (at 10 mol/min), the reduction of renal arterial pressure to 90 mm Hg had no effect on the glomerular filtration rate, whereas, during infusion of the H antagonist, the glomerular filtration rate fell significantly when renal arterial pressure was reduced to 90 mm Hg. Infusion of histamine (1 μg/kg per min) with increasing amounts of cimetidine, chlorpheniramine, diphenhydramine, or pyrilamine resulted in virtually identical dose-dependent decreases in histamine-induced renal vasodilation. However, even with 10 mol/min cimetidine or 10 mol/min chlorpheniramine, diphenhydramine, or pyrilamine, a significant histamine-induced renal vasodilation was observed. Thus, the amount of H antagonist required to inhibit histamine activation of H receptors is the same as needed to block autoregulation. Finally, renal vascular reactivity as estimated by acetylcholine-induced vasodilation was not substantially affected by chlorpheniramine or by pyrilamine. These observations provide evidence in support of a role for histamine as a chemical mediator of renal autoregulation. 1 2 1 2 2 1 1 1 1 1 -5 -5 -5 -5 -5
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    Digital Object Identifier (doi)

    Author List

  • Banks RO; Inscho EW; Jacobson ED
  • Start Page

  • 527
  • End Page

  • 535
  • Volume

  • 54
  • Issue

  • 5