REDUCED BASAL NO-MEDIATED DILATION AND DECREASED ENDOTHELIAL NO-SYNTHASE EXPRESSION IN CORONARY VESSELS OF SPONTANEOUSLY HYPERTENSIVE RATS

Basal vasomotor tone in coronary Vessels is, in part, maintained by ni tric oxide (NO) production by endothelial constitutive NO synthase (ec NOS). Alteration of coronary circulation observed in left ventricular hypertrophy secondary to hypertension could be associated with a decre ase in NO production. The aim of this study was to measure: (1) corona ry now in the Langendorff-perfused heart model at baseline, after maxi mum vasodilation in response to adenosine (10(-5) M), after endotheliu m-dependent vasodilation in response to bradykinin (10(-8) M) and afte r ecNOS inhibition by nitro-L-arginine methyl ester (L-NAME) (10(-4) M ); (2) medial thickening of coronary microvessels and perivascular col lagen on histological heart sections; and (3) ecNOS expression by immu nohistochemical staining in these vessels using 20-week-old spontaneou sly hypertensive (SHR) and Wistar-Kyoto control rats (WKY). These meas urements were determined by computer-directed color analysis. When SHR were compared with WKY rats, we found: (1) a decrease in basal flow ( 10.1 +/- 0.6 v 15.3 +/- 1.2 ml/min/g, n = 10, P<0.001), in maximum now (15.4 +/- 9.7 v 24.3 +/- 1.3 ml/min/g, n = 10, P<0.001), in bradykini n-induced now increment (1.5 +/- 0.3 v 2.6 +/- 0.3 ml/min/g, n = 5, P< 0.05) and in L-NAME-sensitive flow (3.3 +/- 0.6 v 6.3 +/- 0.9 ml/min/g , n = 7, P<0.05); (2) an increase in medial thickness (9.4 +/- 0.6 v 5 .4 +/- 0.3 mu m, n = 8, P<0.001) and in perivascular collagen area (15 09 +/- 311 v 462 +/- 120 mu m(2), n = 8, P<0.01) of coronary arteriole s: and (3) a decrease in ecNOS expression in the endothelium (ecNOS-st ained cross-sectional area in arterioles: 40.0 +/- 9.1 v 84.6 +/- 9.0 mu m(2), n = 7, P<0.005). These results suggest that in SHR the decrea se in basal coronary flow can be related to a structural alteration of the microvessels with an increase of perivascular collagen but also t o a decrease in ecNOS expression which might be associated with reduce d NO production. (C) 1997 Academic Press Limited.