Captopril administration has been shown to result in the release of prostaglandins (PGs) in experimental animals and patients. Also, PGs, particularly prostacyclin (PGI2), have been shown to stimulate left ventricular receptor reflexes. Thus, the hypothesis that captopril administration results in sensitization of left ventricular reflexes via increased circulating levels of PGs was tested in conscious instrumented dogs. Left ventricular reflexes were stimulated by injecting veratridine into the left circumflex coronary artery through a nonocclusive catheter. Under control conditions, injection of veratridine resulted in a decrease in mean arterial pressure of -25 ± 4.7% from a base line of 97 ± 4.7 mm Hg and a decrease in heart rate of -28 ± 3.7% from a base line of 91 ± 6.6 beats/min. After administration of captopril, veratridine injection resulted in a decrease in mean arterial pressure of -43 ± 4.9% and a decrease in heart rate of -51 ± 8.5%; both significantly greater effects than before captopril (P < .05); N = 7). Subsequent administration of the cyclooxygenase inhibitor, indomethacin (5 mg/kg), in the presence of captopril reversed the potentiation of the response to veratridine. Thus, after indomethacin, injection of veratridine decreased mean arterial pressure -29 ± 4.4% and decreased heart rate -28 ± 4.1%; changes not significantly different from the control response. Similar findings were observed in a separate set of experiments in which heart rate was held constant by cardiac pacing (N = 6). Also, in a separate but similar set of experiments (N = 5), administration of indomethacin vehicle after captopril had no significant effect on the captopril potentiation of the hypotension and bradycardia to intracoronary veratridine. In a fourth set of experiments, the response to two doses of intracoronary veratridine were tested before and during intracoronary infusion of PGI2 (10-50 ng/kg/min). Infusion of PGI2 resulted in a profound potentiation of the veratridine responses. Thus, PGI2 or captopril administration both potentiate the effects of left ventricular reflex stimulation with veratridine in conscious dogs. The captopril potentiation is reversed after cyclooxygenase inhibition and is thus most likely a result of endogenous PG synthesis. This study suggests that endogenously released PGs may sensitize left ventricular receptors in conscious dogs.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1988|
ASJC Scopus subject areas
- Molecular Medicine