Potentiation of pressor responses to serotonin by ketamine in isolated perfused rat mesentery.
The effects of ketamine on vasoconstrictor responses to periarterial sympathetic nerve stimulation (PNS), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) were studied in normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The isolated mesenteric arteries were perfused at a constant rate (5 ml/min), and the perfusion pressure was recorded. The pressor responses to PNS (8 Hz, 2 ms, 30 s) were augmented by ketamine (2 X 10(-5) and 10(-4) M) in WKY and SHR. Those to intraarterially infused NE (3 X 10(-10) M) were statistically unaltered. However, in three of seven arterial preparations from WKY and in six of nine preparations from SHR, ketamine (2 X 10(-5) and 10(-4) M) decreased the pressor responses to NE. In contrast, the responses to intraarterial 5-HT (1.3 X 10(-9) mol) were potentiated by ketamine (2 X 10(-5) and 10(-4) M) in SHR and WKY--to a much greater extent in SHR. Fractional release of tritium by PNS from isolated mesenteric arteries previously labeled with 1-[7,8-(3)H]NE (10(-7) M) was unaltered by ketamine (10(-4) M) in SHR and WKY. Cocaine (10(-5) M) prevented the ketamine-induced potentiation of PNS and 5-HT responses. Ketamine as well as cocaine inhibited the accumulations of [3H]5-HT and [3H]NE in intact mesenteric arteries from SHR and WKY to a comparable extent. In tissues denervated by 6-hydroxydopamine, the accumulation of 5-HT was about 70% (WKY) and 60% (SHR) of those in intact tissues, whereas that of NE was about 11% (WKY) and 9% (SHR).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology; D003714:Denervation; D004558:Electric Stimulation; D005110:Extracellular Space / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000494:pharmacology*
D012701:Serotonin; D007649:Ketamine; D003042:Cocaine; D009638:Norepinephrine