Possible role of an endogenous opiate in the cardiovascular effects of central alpha adrenoceptor stimulation in spontaneously hypertensive rats.
In unanesthetized sponatneously hypertensive rats (SHR), naloxone (0.5--2 mg/kg ip.) or naltrexone (2 mg/kg) inhibited the hypotension and bradycardia produced by clonidine (5--20 micrograms/kg iv.). Chronic treatment of SHR with clonidine (3 x 20 micrograms/kg/day orally for 12 days) reduced blood pressure and heart rate and these effects were acutely reversed by a single injection of naloxone. Naloxone also reversed the hypotension produced by a single injection of alpha-methyldopa (50--300 mg/kg ip.). In pentobarbital-anesthetized SHR, the hypotension and bradycardia produced by 5 micrograms/kg of clonidine were inhibited either by naloxone (2 mg/kg) or by yohimbine (1 mg/kg ip.). Morphine (0.33 mg/kg iv.) also reduced blood pressure and heart rate in these animals but these effects were only antagonized by naloxone and not by yohimbine. In conscious and anesthetized normotensive Wistar Kyoto rats, the reduction in blood pressure and heart rate by clonidine or alpha-methyldopa were smaller than in SHR, and these effects were not influenced by naloxone. These results confirm and extend earlier observations and suggest the existence of an "opioidergic" component in the antihypertensive action of central alpha adrenoceptor stimulants in SHR. They also show that a similar mechanism is either absent or inactive in the normotensive Wistar Kyoto rats.
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004723:Endorphins / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008750:Methyldopa / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D004723:Endorphins; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011957:Receptors, Opioid; D015016:Yohimbine; D009270:Naloxone; D008750:Methyldopa; D009271:Naltrexone; D009020:Morphine; D003000:Clonidine