(Circulation. 1995;91:2415-2422.)
© 1995 American Heart Association, Inc.
Articles |
Age and Hypertension Differently Affect Coronary Contractions to Endothelin-1, Serotonin, and Angiotensins
From the Department of Research, Laboratory of Vascular Research, University Hospital Basel (M.R.T., T.F.L.) and the Department of Medicine, Division of Cardiology, University Hospital Bern (T.F.L.), Switzerland.
Correspondence to Thomas F. Lüscher, MD, Division of Cardiology, Inselspital, CH-3010 Bern, Switzerland.
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°C, 95%
O2/5% 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 SHR 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 (AT1) 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
-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.
Key Words: angiotensin • enzymes • benazeprilat • valsartan • endothelium-derived factors
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