Influence of Mode of Contraction on the Mechanism of Acetylcholine-Mediated Relaxation of Coronary Arteries from Normotensive and Spontaneously Hypertensive Rats

1. Endothelium-dependent acetylcholine-mediated relaxations of small coronary arteries (∼200 μm internal diameter) from 20 weeks old spontaneously hypertensive rats (SHR) and normotensive Wistar—Kyoto (WKY) controls were compared under pressurized no-flow conditions after the development of myogenic tone or constriction with the thromboxane A₂ mimetic U46619.

2. Relaxations of WKY and SHR arteries following development of myogenic tone did not differ and were not significantly influenced by indomethacin alone (10 μmol/l) or in combination with N_ω-nitro-l-arginine (l-NNA, 0.1 mmol/l). Maximum relaxations were significantly attenuated by 30 mmol/l K⁺ in the SHR, from 85 ± 7% (n = 11) to 20 ± 8% (n = 8), P < 0.001, and in the WKY from 86 ± 5% (n = 9) to 39 ± 14% (n = 8), P < 0.01.

3. Relaxations following constriction with U46619 were also similar in both rat strains. Maximum relaxations were 50 ± 11% (n = 8) in SHR and 60 ± 7% (n = 6) in WKY. Indomethacin did not influence these relaxations. The combination of indomethacin and l-NNA attenuated relaxations in WKY (P < 0.01), but in the SHR the attenuation did not achieve statistical significance (P = 0.07) compared with controls; the maximum responses were reduced to 25 ± 7% (n = 8) and 14 ± 11% (n = 6) in the SHR and WKY respectively, but only in the WKY was this reduction significant (P < 0.05).

4. These data demonstrate that, under control conditions, SHR and WKY coronary arteries relax equally effectively, regardless of mode of contraction, and also that the mechanism of acetylcholine-mediated relaxation differs according to the mode of contraction. Acetylcholine relaxes myogenic tone by a K⁺-sensitive mechanism in both WKY and SHR, consistent with a role for endothelium-derived hyperpolarizing factor; NO contributes substantially to the relaxation of U46619-induced tone by acetylcholine in the WKY, but to a diminished extent in the SHR.

5. These data indicate that the choice of vasoconstrictor agent is of critical concern when assessing mechanisms of endothelium-dependent relaxation and abnormalities thereof in hypertension.