Serotonin and the renal blood supply: role of prostaglandins and the 5HT-2 receptor.
Serotonin (5HT) has been reported to increase, to decrease, or not to change renal blood flow. We postulated that prostaglandin release in response to 5HT acted as a confusing variable, and tested the hypothesis by comparing infusions of serotonin and angiotensin into one renal artery of 14 anesthetized dogs before and after indomethacin administration. Renal blood flow (Q, by EM flow-meter) responses to 5HT were routinely biphasic, an initial sharp decrease followed by a gradual increase which stabilized well above baseline at three to six minutes. Indomethacin, 1 to 2 mg/kg, did not alter the acute Q decrement induced by 5HT but abolished the increase in Q at three to six minutes (P less than 0.001). Instead, sustained vasoconstriction became apparent. Ketanserin reversed the sustained vasoconstrictor effect of 5HT in indomethacin-treated dogs, leading to striking, serotonin-induced vasodilatation. The latter vasodilatation in turn was inhibited by methysergide. Four independent elements, two promoting vasoconstriction and two vasodilatation, are suggested. One vasodilator response is abolished by prostaglandin synthetase inhibition and the other by methysergide, a complex 5HT receptor blocker. The sustained vasoconstrictor response is blocked by ketanserin, suggesting an action on the 5HT-2 receptor. The initial, transient vasoconstrictor response is resistant to the blockers employed. These complex interactions may account for the variability in reported responses of the renal blood supply to serotonin.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D008784:Methysergide / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D011985:Receptors, Serotonin; D000804:Angiotensin II; D012701:Serotonin; D007650:Ketanserin; D007213:Indomethacin; D008784:Methysergide