Effect of a serotonin blocking agent on renal hemodynamics in the normal rat.
These studies were designed to explore the effects of ketanserin (K), a serotonergic S2-receptor blocker on glomerular filtration rate (GFR), renal plasma flow (RPF) and autoregulation of renal blood flow (RBF) in the normal, anesthetized rat. Two doses of ketanserin were used: a high dose that, in addition to its serotonin blocking effect, possessed alpha 1-adrenergic blocking capacities; and a low dose that acted only as a serotonin S2 blocking agent. The effects of the high dose were compared to the effects of phenotolamine. Both the high dose of K and phentolamine resulted in a similar fall of systemic blood pressure from 117 +/- 4 to 78 +/- 3 and from 121 +/- 4.5 to 76 +/- 5 mm Hg, respectively (P less than 0.01). Despite this fall, GFR and RPF remained unchanged from 2.36 +/- 0.16 +/- to 2.26 +/- 0.12 ml/min, and from 5.33 +/- 0.41 to 5.76 +/- 0.5 ml/min with K, while both parameters significantly decreased with phentolamine. A remarkable preservation of the autoregulation of RBF until a renal perfusion pressure (RPP) of 70 to 75 mm Hg was noted with K, but not with phentolamine or Ringer infusion. With the low dose of K, a significant rise in GFR and PAH clearance was noted, from 2.12 +/- 0.17 to 2.59 +/- 0.18 and from 4.81 +/- 0.35 to 5.66 +/- 0.48 ml/min, respectively (P less than 0.05). A similar preservation of autoregulation of RBF was observed. Our studies suggest that in the pressure ranges below normal autoregulation of RBF in the rat, serotonin blockade is associated with maintenance of both GFR and RBF.
Lameire
N H
NH
Department of Medicine, University Hospital, Ghent, Belgium.
Matthys
E
E
Kesteloot
D
D
Waterloos
M A
MA
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D007650:Ketanserin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D012702:Serotonin Antagonists; D007650:Ketanserin; D010646:Phentolamine