Differences in vasodilating action between ketanserin, a 5-HT2-serotonergic receptor antagonist, and terazosin, an alpha 1-adrenoceptor antagonist, in anesthetized rabbits.
It has not yet been demonstrated clearly whether the antihypertensive action of ketanserin is due to 5-hydroxytryptamine type-2 (5-HT2)-serotonergic receptor blockade or to alpha 1-adrenergic receptor blockade. The present study was performed to evaluate in vivo the antihypertensive action of ketanserin in comparison with that of terazosin, a selective alpha 1-adrenoceptor antagonist. The changes of renal blood flow (RBF) after intrarenal injection of phenylephrine, 5-HT, or angiotensin II were measured in anesthetized rabbits. RBF responses induced by these vasoconstrictors with or without pretreatment with ketanserin (0.2, 1.0, and 5.0 mg/kg, i.v.) or terazosin (0.04, 0.2, and 1.0 mg/kg, i.v.) were examined. Following intrarenal injection, RBF decreased by 20.8%, 22.7%, and 23.0% respectively, without ketanserin and also decreased by 21.0%, 21.6%, and 24.4%, respectively, without terazosin. Following pretreatment with a small dose of ketanserin or terazosin, the vasoconstricting effects of phenylephrine were attenuated by 20% or 62% (delta% changes in RBF), respectively. The effects of 5-HT on RBF responsiveness were blocked by ketanserin in a dose-dependent manner. Ketanserin did not modify the RBF responses to angiotensin II. These findings indicate that the antihypertensive effect of ketanserin, to a certain extent, depends on the blockade of the 5-HT2-serotonergic receptor in addition to that of the alpha 1-adrenoceptor, whereas the renin-angiotensin system is not involved in the hypotensive effects of ketanserin.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; C041226:Terazosin; D007650:Ketanserin; D011224:Prazosin