Naloxone pretreatment blocks the hypotensive effects of atenolol in SHR and WKY rats.
The present study examined the interaction of opioidergic systems in the hypotensive action of atenolol. Anesthetized, adult spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were instrumented to monitor blood pressure and heart rate. Atenolol (100 micrograms/kg, i.v.) produced a decrease in blood pressure of similar magnitude in both SHR and WKY rats. However, the bradycardia was greater in SHR. Pretreatment with naloxone (0.1 mg/kg, i.v.) 15 min prior to the administration of atenolol completely prevented the hypotensive response in SHR and decreased the maximum hypotensive response by approximately 50% in WKY rats. The atenolol-induced bradycardia was unaffected in both groups of animals. Additionally, pretreatment with yohimbine, an alpha 2-receptor antagonist, inhibited the hypotensive response of atenolol in SHR. Collectively, these results suggest an interaction between opioidergic and catecholaminergic systems as a possible site of action of antihypertensive drugs.
Laskey
R E
RE
Cardiovascular Pharmacodynamics Laboratory, College of Pharmacy, University of Georgia, Athens.
Jones
L F
LF
Tackett
R L
RL
D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors*; D001262:Atenolol / Q000037:antagonists & inhibitors*; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015016:Yohimbine / Q000494:pharmacology
D000959:Antihypertensive Agents; D015016:Yohimbine; D009270:Naloxone; D001262:Atenolol