Naloxone augments sympathetic outflow induced by centrally administered endothelin in conscious rabbits.
We examined the role of endogenous opioids in cardiovascular and neurohormonal responses to intracerebroventricular (icv) endothelin-1 (ET-1) in conscious rabbits. With or without pretreatment with intravenous naloxone (1 mg/kg), the effects of icv ET-1 (25 pmol/kg) on cardiovascular and neurohormonal responses were examined. ET-1 (icv) caused significant increases in mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), plasma catecholamines, and vasopressin levels. Naloxone pretreatment significantly augmented the increases in MAP and RSNA induced by icv ET-1. To clarify the mechanism of these effects, we also examined the effects of naloxone and naloxone methobromide, which does not cross the blood-brain barrier, on baroreceptor reflex. Intravenous naloxone (1 mg/kg) attenuated the baroreflex sensitivity assessed by RSNA (Smax: -9.9 +/- 1.7 vs. -6.9 +/- 1.2, P < 0.01); however, intravenous naloxone methobromide failed to alter the baroreflex sensitivity. Furthermore, in sinoaortic-denervated rabbits, naloxone pretreatment did not affect the increase in MAP induced by (icv) ET-1. These results suggest that intravenous naloxone acts in the central nervous system to attenuate the baroreflex sensitivity, which might augment the increases in MAP and RSNA induced by icv ET-1 in conscious rabbits.
Matsumura
K
K
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Abe
I
I
Fukuhara
M
M
Tominaga
M
M
Tsuchihashi
T
T
Kobayashi
K
K
Fujishima
M
M
D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D004357:Drug Synergism; D016232:Endothelins / Q000494:pharmacology*; D006728:Hormones / Q000097:blood; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects*
D016232:Endothelins; D006728:Hormones; D009270:Naloxone