Attenuation of vasopressin-mediated coronary constriction and myocardial depression in the hypoxic heart

W. A. Boyle, L. D. Segel

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Abstract

To investigate the ability of arginine vasopressin (AVP) to compete with metabolic vasodilatory factors in the coronary circulation, we examined the coronary vascular and myocardial effects of AVP in isolated working rat hearts during normoxic and hypoxic perfusion. In normoxic hearts, AVP treatment (777±67 pg/ml) reduced coronary flow by 38.4±2.6%. Myocardial function was also significantly decreased by AVP whereas efficiency significantly increased. In contrast, the same dose of AVP administrered to hypoxic hearts resulted in substantially smaller effects on coronary flow (-11.5±2.8%), myocardial function, and efficiency. In hearts treated first with AVP and then with hypoxia, the greater degree of coronary vasodilation compared with that observed in hearts treated with hypoxia alone also indicated an antagonizing effect of hypoxia on AVP-mediated coronary constriction. It was also noted that the hypoxia treatment alone resulted in reductions of O2 supply and consumption identical to those produced by AVP treatment during normoxia. However, hypoxia was associated with a significantly greater effect on myocardial function and, in contrast to the effect of AVP, a marked reduction in efficiency. The rate of lactate release was greater during hypoxia alone (2.07±0.08 μmol/min) than with AVP treatment during normoxia (0.76±0.05 μmol/min). These results indicate that the effect of AVP on the coronary vessels, as well as its effect on the myocardium, is significantly attenuated during hypoxia. In addition, AVP-constricted vessels appear to retain considerable vasodilatory reserve despite evidence of ischemic conditions. Thus, although the effects of AVP resemble ischemia, the increased efficiency and the relatively small effect of AVP on contractile function, as well as the preserved vasodilatory reserve, suggest otherwise. A physiological explanation for these observations is proposed wherein the constricting effects of AVP modulate the effects of autoregulatory factors such that blood flow requirements are minimized while allowing preservation of adequate blood flow for vital tissue function.

Original languageEnglish
Pages (from-to)710-721
Number of pages12
JournalCirculation research
Volume66
Issue number3
DOIs
StatePublished - 1990

Keywords

  • Coronary constriction
  • autoregulation
  • myocardial contraction
  • myocardial ischemia
  • vasopressin

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