Key result
Glibenclamide causes greater coronary flow reduction in hypertensive rats, correlating with LVH.
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Demonstrates increased basal activation of coronary KATP channels in hypertensive rats, suggesting a vital compensatory role in maintaining myocardial perfusion during cardiac hypertrophy.
OBJECTIVE: To determine whether opening of coronary vascular adenosine 5'-triphosphate (ATP)-sensitive potassium (KATP) channels is involved in the maintenance of resting coronary flow in hypertrophied hearts. METHODS: We examined the effects of glibenclamide, a selective inhibitor of KATP channels, on basal coronary vascular tone in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Using a Langendorff system, the hearts from WKY rats and SHRs were isolated and perfused with oxygenated Krebs-Henseleit solution at a constant perfusion pressure of 60 and 100 mmHg respectively. RESULTS: Basal coronary flow and myocardial oxygen consumption (MV02) were similar in SHRs and WKY rats. The percentage decreases in coronary flow with glibenclamide at graded doses were greater (P < 0.01) in SHRs than in WKY rats (n = 8), whereas the percentage decreases in MV02 with glibenclamide were similar in the two groups. The decreases in coronary flow caused by U46619 (a thromboxane A2-mimetic agent) were similar in SHRs and WKY rats (n = 4). The increase in coronary flow caused by pinacidil (a KATP opener) was greater in SHRs than in WKY rats; glibenclamide prevented the pinacidil-induced increase in coronary flow in both SHRs and WKY rats. There was a significant positive correlation between the glibenclamide-induced decrease in coronary flow and the degree of left ventricular hypertrophy (r = 0.54, P < 0.05). CONCLUSION: Our results suggest that the basal opening state of coronary vascular KATP channels is activated to a greater extent in SHRs than WKY rats, which may contribute to the maintenance of basal myocardial perfusion in hypertrophied hearts.
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Numaguchi et al. (1996) studied Hypertension and left ventricular hypertrophy. Glibenclamide (selective KATP channel inhibitor), U46619, and pinacidil vs. Wistar-Kyoto (WKY) rats vs spontaneously hypertensive rats (SHRs) was evaluated on Percentage decrease in basal coronary flow with glibenclamide (r = 0.54 (correlation with LV hypertrophy), p=<0.01). Glibenclamide caused a greater percentage decrease in coronary flow in spontaneously hypertensive rats than in Wistar-Kyoto rats (P<0.01), correlating with left ventricular hypertrophy (r=0.54, P<0.05).
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