Impaired endothelium-dependent regulation of ventricular relaxation in pressure-overload cardiac hypertrophy.
BACKGROUND
Endothelium-derived nitric oxide (NO) selectively enhances myocardial relaxation and may benefit diastolic function. Left ventricular hypertrophy (LVH) is characterized by abnormal myocardial relaxation and endothelial dysfunction. We investigated endothelium-dependent regulation of LV relaxation in moderate pressure-overload LVH induced by aortic banding in guinea pigs.


RESULTS
Isolated ejecting hearts of banded or sham-operated animals (shams) were studied. The specific agonists for endothelial release of NO, bradykinin (10 nmol/L), and substance P (100 nmol/L) both induced earlier onset of LV relaxation in shams (time to LV dP/dt(min) [tdP/dt(min)], -13.4+/-3.0 and -10.4+/-2.5 ms, respectively) without altering peak LV pressure or LV dP/dt(max). Neither agent altered tdP/dt(min) in banded animals. The ACE inhibitor captopril (1 micromol/L) also selectively reduced tdP/dt(min) in shams via a bradykinin/NO-dependent mechanism but had no effect in banded animals. An exogenous NO donor, sodium nitroprusside (0.1 micromol/L), selectively reduced tdP/dt(min) to a similar extent in both shams and banded animals. Endothelial-type NO synthase (eNOS) protein expression in whole LV homogenate was unaltered in banded animals.


CONCLUSIONS
Endothelium-dependent enhancement of LV relaxation is impaired in moderate pressure-overload LVH, despite a preserved response to exogenous NO. This is not accounted for by altered eNOS expression. These abnormalities may contribute to diastolic dysfunction in LVH.
MacCarthy
P A
PA
Department of Cardiology, University of Wales College of Medicine, Cardiff, UK.
Shah
A M
AM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001920:Bradykinin / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006168:Guinea Pigs; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013373:Substance P; D002216:Captopril; D001920:Bradykinin