DIRECT EFFECTS OF INDORENATE AND 8-OH-DPAT ON THE BLOOD-PRESSURE OF PITHED RATS

Indorenate is a 5-HT1A receptor agonist with antihypertensive properties. This study was aimed to determine if indorenate, like other 5-HT1A receptor agonists, may also interact with a-adrenoceptors. Therefore, the effects of indorenate and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; which has affinity for 5-HT1A receptors and, to a lesser extent, for alpha(1)-adrenoceptors) on the blood pressure of pithed rats were compared. Both compounds produced dose-dependent increases in blood pressure; 8-OH-DPAT was the most potent whereas indorenate produced a higher maximum effect. Metitepine (a mixed 5-HT1/5-HT2 receptor antagonist), but not pindolol (a beta-adrenoceptor and 5-HT1 receptor blocker), antagonized the presser responses produced by both agonists; only the presser effects of 8-OH-DPAT, however, were antagonized by prazosin (an alpha(1)-adrenoceptor antagonist). Interestingly, ketanserin (a 5-HT2 and alpha(1)-adrenoceptor blocker) strongly antagonized the presser responses to indorenate whereas only a slight inhibition of 8-OH-DPAT responses was observed. Further, in pithed rats intravenously infused with norepinephrine (NE), 8-OH-DPAT, but not indorenate, produced dose-dependent hypotensive effects and both compounds were inactive in rats infused with quipazine. In conclusion, 8-OH-DPAT behaved as a partial agonist at alpha(1)-adrenoceptors whereas indorenate produced presser effects probably due to stimulation of 5-HT2 receptors. Thus, 8-OH-DPAT, but not indorenate, showed activity at alpha(1)-adrenoceptors in the pithed rat. (C) 1994 Wiley-Liss, Inc.