Relationship Between Perfusion Pressure and Coronary Vasoreactivity in Saline Perfused Hearts Isolated from Normotensive and Spontaneously Hypertensive Rats: Role of Endothelium

Although reduced endothelium-dependent coronary vasodilation is a consistent finding in patients with hypertension, studies in perfused hearts isolated from spontaneously hypertensive rats (SHR) lead to controversial results. One possible explanation is that coronary vascular reactivity in SHR hearts were studied at different fixed perfusion pressure levels, which were outside the arterial blood pressure range found in these animals. Therefore, the objective of the present experiments was to systematically study the effect of an endothelium-dependent (serotonin) and endothelium-independent (sodium nitroprusside, SNP) vasodilator on coronary flow rate at a wide range of perfusion pressure levels (55 to 130 mmHg) in saline perfused hearts isolated from normotensive (NWR) and SH rats. The pressure-flow relationship showed coronary flow autoregulation at different pressure levels in the two groups (55 to 90 mmHg in NWR hearts and 110 to 130 mmHg in SHR hearts). At a maximally effective concentration (104M) coronary vasodilation by both serotonin and SNP was significantly more pronounced in NWR than in SHR hearts at every perfusion pressure level studied. At pressure levels of 55 and 70 mmHg, neither serotonin nor SNP caused any vasodilation in SHR hearts. Analysis of full dose-response relationship to serotonin at various pressure levels revealed that (1) in both groups the extent of coronary vasodilation increased with elevation of perfusion pressure, and (2) maximal response was significantly higher in NWR hearts at all pressure levels. These data show that coronary reactivity to serotonin and SNP is perfusion pressure dependent in both NWR and SHR heart. Since "impaired" coronary vasodilation was observed in SHR hearts with both the endothelium-dependent and-independent vasodilators, the most probable cause of reduced vasodilation is lower active vascular tone and/or reduced smooth muscle reactivity to nitric oxide, rather than impaired endothelium-dependent vasorelaxation.