Endogenous nitric oxide prevents myocardial ischemia in patients with hypertension and left ventricular hypertrophy.
BACKGROUND
Left ventricular hypertrophy (LVH) caused by chronic pressure overload is associated with increased risk of myocardial ischemia without epicardial coronary artery disease. We aimed to test the hypothesis that endogenous nitric oxide (NO) prevents myocardial ischemia in patients with LVH.


METHODS
Epicardial coronary blood flow (Doppler wire and quantitative coronary arteriography) and myocardial lactate metabolism (paired arterial and coronary sinus blood sampling) were measured in 12 patients with hypertension, LVH, and angiographically normal epicardial coronary arteries and in 7 control subjects. Measurements were done under 3 pacing protocols: with no treatment (control), with intracoronary N(G)-monomethyl-L-arginine (L-NMMA; NO synthesis inhibitor), and with intracoronary L-arginine (NO substrate).


RESULTS
In control subjects the myocardial lactate extraction ratio was normal and stable during the 3 pacing protocols. In contrast, lactate uptake was significantly decreased from 0.21 +/- 0.05 to 0.10 +/- 0.06 (P <.05) during L-NMMA pacing in patients with LVH; in 6 of them, lactate production was demonstrated. After L-arginine administration, the lactate extraction ratio during pacing was normalized (0.18 +/- 0.04) and lactate production was not observed in any patient. The level of myocardial lactate uptake at peak pacing after L-NMMA was correlated with that under untreated condition (P <.0001).


CONCLUSIONS
In patients with hypertension, LVH, and angiographically normal coronary arteries, inhibition of endogenous NO synthesis in the coronary circulation unmasked myocardial ischemia during tachycardia, and L-arginine reversed the adverse effects of L-NMMA. Although the precise mechanism remains to be determined, our results suggest that constitutive NO in the coronary circulation plays an anti-ischemic role in this population.
Mohri
Masahiro
M
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. mmohri@med.kyushu-u.ac.jp
Ichiki
Toshihiro
T
Hirooka
Yoshitaka
Y
Takeshita
Akira
A
D000368:Aged; D006328:Cardiac Catheterization; D003326:Coronary Circulation; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications*; D017379:Hypertrophy, Left Ventricular / Q000150:complications*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000627:therapeutic use*
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019344:Lactic Acid