Endogenous opioids and opiate antagonists modulate the blood pressure of the spontaneously hypertensive rat.
Endogenous opioids have been implicated as modulators of the central nervous system regulation of blood pressure and heart rate. Whether these neuropeptides participate in blood pressure regulation in hypertension is unknown. To begin to study this question, we examined the response to opiate antagonists and agonists in the spontaneously hypertensive rat (SHR) and the normotensive Wistar-Kyoto (WKY) rat. The long-acting opiate antagonist naltrexone, 2.5 micrograms/kg, was injected into the lateral ventricle of the brain in awake, freely-moving SHR and produced a significant 19 mmHg decrease in mean arterial blood pressure compared to basal blood pressure (p less than 0.01); a decrease was not observed at a two logarithm lower dose. In contrast, naltrexone had no effect on the blood pressure of normotensive Wistar-Kyoto (WKY) rats. To evaluate a possible regulatory role for the predominantly kappa receptor active opioids, alpha- and beta-neo-endorphin, 10 micrograms each, was administered to SHR on separate days by intracerebroventricular injection. alpha- and beta-neo-endorphin caused significant decreases in mean arterial blood pressure of 11 and 9 mmHg respectively, effects reversed by pre-treatment with the opiate antagonist, naloxone. Heart rate was unaffected by any of the injected opioids or antagonists. Our naltrexone results support the hypothesis that an endogenous opioid(s) contributes to the hypertensive state of the SHR. Additionally, alpha- and beta-neo-endorphin can lower blood pressure in this model.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004347:Drug Interactions; D004723:Endorphins / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D001615:beta-Endorphin / Q000031:analogs & derivatives*
D004723:Endorphins; D011498:Protein Precursors; D009270:Naloxone; D009271:Naltrexone; D001615:beta-Endorphin; C025681:alpha-neoendorphin; C030719:beta-neo-endorphin