Endogenous and exogenous coronary vasodilatation are attenuated in cardiac hypertrophy: a morphological defect?

Reactive hyperaemia (RH) following brief ischaemia is reduced in hypertrophied hearts, and this may contribute to reduced coronary flow reserve. We studied vasodilatation during RH and in response to exogenous stimuli in control and hypertrophied hearts and explored the mechanisms underlying RH. Vascular reactivity was assessed in isolated hypertrophied hearts (55+/-3 days after aortic banding or sham operation) by constructing dose-response curves to acetylcholine (ACh), sodium nitroprusside (SNP) and adenosine. Reactive hyperaemic vasodilatation was assessed after global ischaemia (5-120 s) in the presence/absence of L -NAME, 8-phenyltheophylline (8-PT) and glibenclamide. Purine release and NO overflow in the coronary perfusate were analysed. Aortic constriction increased heart/body weight ratio (47%), myocyte size (19%) and arteriolar wall thickness (51%), all P<0.01. Coronary reserve was reduced in hypertrophy (105+/-8%v 182+/-12%, P<0.01). Dose response curves for ACh, SNP and adenosine were reduced in hypertrophy (69%, 86% and 68%, all P<0.01) v shams; however ED(50)values were unchanged. The peak flow and duration of RH were also attenuated (50%, P<0.001) in hypertrophy. While purine washout during RH was related to the duration of preceding ischaemia, nitrate washout was not. RH experiments in the presence of L -NAME, 8-PT and glibenclamide indicated that RH is mediated by combined actions of K(ATP)channels>adenosine>NO in both groups. RH is mediated by similar mechanisms in control and hypertrophied hearts. All vasodilatation was similarly attenuated in hypertrophy, independent of endothelial activation. We hypothesize that increased arteriolar wall thickness may limit vasodilator responses to all stimuli in hypertrophy.