HETEROGENEITY OF GLYCERYL TRINITRATE RESPONSE IN ISOLATED BOVINE CORONARY-ARTERIES

Factors determining heterogeneity of response to glyceryl trinitrate i n coronary microvessels have been extensively documented in recent yea rs, but determinants of heterogeneity between conduit and large resist ance vessels are poorly understood. The current study has characterise d heterogeneity to glyceryl trinitrate and other vasodilators in bovin e isolated proximal (4.5 mm i.d.) and distal (0.5 mm i.d.) segments of left anterior descending artery. Compared with proximal segments, dis tal segments were less responsive to glyceryl trinitrate and sodium ni troprusside, equi-responsive to S-nitroso-N-acetylpenicillamine, and m ore responsive to isoprenaline. Heterogeneity to glyceryl trinitrate w as unaffected by the presence of the thiols (cysteine or N-acetylcyste ine, 100 mu M). The results are interpreted as evidence that heterogen eity of vascular responsiveness to glyceryl trinitrate reflects impair ment in the small artery of the cellular events which precede activati on of the cyclic GMP pathway. An implication is that the impairment is not a consequence of limited thiol availability, and in this respect the cellular mechanism of heterogeneity differs from those proposed fo r the coronary microvasculature.