TY - JOUR
T1 - Hormone interactions in the isolated rabbit heart. Synthesis and coronary vasomotor effects of prostaglandins, angiotensin, and bradykinin
AU - Needleman, P.
AU - Marshall, G. R.
AU - Sobel, B. E.
PY - 1975
Y1 - 1975
N2 - In the present study, the synthesis and degradation of several potent vasoactive substances influencing coronary resistance were characterized in the isolated perfused rabbit heart. Prostaglandin synthetase activity, angiotensin converting enzyme activity, and bradykininase activity (without angiotensinase) were observed. A prostaglandin E2 like substance appeared to be the endogenous mediator of the coronary vasodilation produced by bradykinin and angiotensin II (AII). The concentration of this prostaglandin like substance in the coronary venous effluent was directly proportional to the concentration of the coronary vasodilator stimulus (bradykinin or AII). The prostaglandinlike substance released and the coronary dilatation produced by the agonists correlated temporally and quantitatively. Abolition of cardiac biosynthesis of the prostaglandinlike substance by indomethacin also abolished the decrease in coronary resistance produced by the agonists. AII, the most potent naturally occurring vasoconstrictor substance, produced a paradoxical coronary vasodilation because it stimulated cardiac prostaglandin biosynthesis, but the direct coronary vasoconstrictor action of AII could be readily unmasked by indomethacin, which blocks prostaglandin synthesis. The nonapeptide SQ-20881 blocked cardiac biosynthesis of AII (from angiotensin I) and enhanced the coronary vascular effects of bradykinin by interfering with bradykininase activity. Similarly, the AII-receptor antagonist, 1-Sar-8-Ile-AII, blocked the coronary vascular effects of AII.
AB - In the present study, the synthesis and degradation of several potent vasoactive substances influencing coronary resistance were characterized in the isolated perfused rabbit heart. Prostaglandin synthetase activity, angiotensin converting enzyme activity, and bradykininase activity (without angiotensinase) were observed. A prostaglandin E2 like substance appeared to be the endogenous mediator of the coronary vasodilation produced by bradykinin and angiotensin II (AII). The concentration of this prostaglandin like substance in the coronary venous effluent was directly proportional to the concentration of the coronary vasodilator stimulus (bradykinin or AII). The prostaglandinlike substance released and the coronary dilatation produced by the agonists correlated temporally and quantitatively. Abolition of cardiac biosynthesis of the prostaglandinlike substance by indomethacin also abolished the decrease in coronary resistance produced by the agonists. AII, the most potent naturally occurring vasoconstrictor substance, produced a paradoxical coronary vasodilation because it stimulated cardiac prostaglandin biosynthesis, but the direct coronary vasoconstrictor action of AII could be readily unmasked by indomethacin, which blocks prostaglandin synthesis. The nonapeptide SQ-20881 blocked cardiac biosynthesis of AII (from angiotensin I) and enhanced the coronary vascular effects of bradykinin by interfering with bradykininase activity. Similarly, the AII-receptor antagonist, 1-Sar-8-Ile-AII, blocked the coronary vascular effects of AII.
UR - http://www.scopus.com/inward/record.url?scp=0016618695&partnerID=8YFLogxK
U2 - 10.1161/01.RES.37.6.802
DO - 10.1161/01.RES.37.6.802
M3 - Article
C2 - 1192572
AN - SCOPUS:0016618695
VL - 37
SP - 802
EP - 808
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 6
ER -