Prostaglandins mediate the increased sensitivity of left ventricular reflexes after captopril treatment in conscious dogs.
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 less than .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).(ABSTRACT TRUNCATED AT 250 WORDS)
Panzenbeck
M J
MJ
Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha.
Tan
W
W
Hajdu
M A
MA
Zucker
I H
IH
D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000494:pharmacology*; D012018:Reflex / Q000187:drug effects*; D014701:Veratridine / Q000494:pharmacology
D011453:Prostaglandins; D014701:Veratridine; D002216:Captopril; D007213:Indomethacin