The role of endocardial endothelium in the modulation of myocardial contraction in the isolated whole heart.
Selective damage to the endocardial endothelium in isolated papillary muscle preparations has been shown to produce an abbreviation of contraction, changes which were also observed following an increase in myocardial cyclic GMP in those preparations. In the present study we have investigated the effects of removing the endocardium and increasing myocardial cyclic GMP on contractile parameters in isolated Langendorff perfused ferret hearts, where the myocardial mass underlying the endocardium is much greater. Selective damage to left ventricular endocardial endothelium without damaging the underlying myocardium was achieved by brief exposure to a weak detergent solution (Triton X-100 0.005% v/v). This resulted in a significant abbreviation of the left ventricular pressure-time curve due to the earlier onset of relaxation, but there was little effect on early systole. The direct intraventricular infusion for 15 minutes of 10 microM sodium nitroprusside, a donor of nitric oxide, or of 1 microM substance P, to stimulate release of endothelium-derived relaxing factor, did not increase myocardial cyclic GMP levels or alter left ventricular contractile performance. Myocardial cyclic GMP levels were significantly increased by 15 minute intracoronary infusions of 10 microM nitroprusside and 1 microM substance P, approximately ten-fold and two-fold respectively. Intracoronary nitroprusside induced an abbreviation of the left ventricular pressure-time curve with an earlier onset of relaxation, but contraction was unaltered by intracoronary substance P. These results show that, in the isolated Langendorff perfused ferret heart, both selective removal of endocardial endothelium and an increase in myocardial cyclic GMP cause an abbreviation of left ventricular pressure and an earlier onset of relaxation with little change in early systole.
Fort
S
S
Department of Pharmacology & Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Lewis
M J
MJ
Shah
A M
AM
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004699:Endocardium / Q000502:physiology*; D004727:Endothelium / Q000502:physiology; D005260:Female; D005289:Ferrets; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D013373:Substance P / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000502:physiology
D009599:Nitroprusside; D009569:Nitric Oxide; D013373:Substance P; D006152:Cyclic GMP