AGE AND HYPERTENSION DIFFERENTLY AFFECT CORONARY CONTRACTIONS TO ENDOTHELIN-1, SEROTONIN, AND ANGIOTENSINS

Background Endothelium-derived substances and the renin-angiotensin system are important regulators of vascular tone. This study was designed to evaluate the effects of age and hypertension on vascular function of rat coronary arteries. Methods and Results Rings of the left anterior descending coronary artery were isolated from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at 12 (younger) and 72 (older) weeks of age and suspended in myographs (37 degrees C, 95% O-2/5% CO2) for isometric tension recording. Systolic blood pressure was higher in SHR than in WKY rats (P<.05) but was unaffected by age in both strains. Active wall tension to KCl 100 mmol/L (mN/mm) was decreased in younger (0.28+/-0.03, n=9) and older SHR (0.49+/-0.06, n=13) compared with age-matched WKY rats (0.87+/-0.05, n=9 and 1.51+/-0.11, n=11, respectively, P<.05). In both strains, active wall tension to endothelin-1 and serotonin increased with age (n=6 to 10, P<.05) but was decreased in younger and older SKR compared with WKY rats (P<.05). Active wall tension induced by angiotensin I 10(-7) mol/L was increased in older SHR (0.19+/-0.04, n=7) compared with younger SHR (0.04+/-0.01, n=9) but was similar in younger and older WKY rats (0.10+/-0.02 versus 0.15+/-0.03, n=6 to 9) and younger SHR. In younger WKY rats and SHR, pretreatment of coronary arteries with benazeprilat 10(-5) mol/L (n=5 for each) almost completely abolished the contractions to angiotensin I 10(-7) mol/L. Active wall tension to angiotensin II 10(-7) mol/L was comparable in all four groups, but compared with the contraction to KCl 100 mmol/L, the response was already increased in younger SHR (29+/-3%, n=9) compared with the younger WKY rats (14+/-3%, n=9, P<.05), but it was unaffected by age in both strains. In vitro treatment of younger WKY rat and SHR coronary arteries with the nonpeptide angiotensin II (AT(1)) receptor antagonist valsartan 10(-5) mol/L (n=3 for each) fully suppressed contractions to angiotensin II 10(-7) mol/L. In contrast, endothelium-independent relaxations to the nitrovasodilator sodium nitroprusside, endothelium-dependent relaxations to acetylcholine, and endothelium-dependent contractions to N-omega-nitro-L-arginine methyl ester were comparable in all four groups of rats. Conclusions In summary, in rat coronary arteries, contractile responses to endothelin-1, serotonin, and KCL increase with age but are decreased by hypertension. In contrast, the L-arginine/nitric oxide pathway remains unaffected. The contractions to angiotensin I markedly increased with increasing duration of hypertension in the SHR only. Despite overall reduced contractile responses of SHR coronary arteries, contractions to angiotensin II were maintained. Hence, aging and hypertension affect contractile responses of rat coronary arteries to vasoconstrictor agonists differently.