Tschudi M R, Lüscher T F
Department of Research, University Hospital Basel, Switzerland.
Circulation. 1995 May 1;91(9):2415-22. doi: 10.1161/01.cir.91.9.2415.
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.
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% 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 omega-nitro-L-arginine methyl ester were comparable in all four groups of rats.
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.
内皮衍生物质和肾素 - 血管紧张素系统是血管张力的重要调节因子。本研究旨在评估年龄和高血压对大鼠冠状动脉血管功能的影响。
从12周龄（年轻）和72周龄（年长）的Wistar - Kyoto（WKY）大鼠和自发性高血压大鼠（SHR）中分离出左前降支冠状动脉环，悬挂于肌张力测定仪中（37℃，95% O₂/5% CO₂）进行等长张力记录。SHR的收缩压高于WKY大鼠（P <.05），但在两种品系中年龄对收缩压均无影响。与年龄匹配的WKY大鼠相比，年轻（0.28±0.03，n = 9）和年长的SHR（0.49±0.06，n = 13）对100 mmol/L KCl的主动壁张力降低（分别为0.87±0.05，n = 9和1.51±0.11，n = 11，P <.05）。在两种品系中，对内皮素 - 1和5 - 羟色胺的主动壁张力均随年龄增加（n = 6至10，P <.05），但与WKY大鼠相比，年轻和年长的SHR均降低（P <.05）。与年轻的SHR相比，年长的SHR（0.19±0.04，n = 7）对10⁻⁷ mol/L血管紧张素I诱导的主动壁张力增加，但年轻和年长的WKY大鼠（0.10±0.02对0.15±0.03，n = 6至9）以及年轻的SHR相似。在年轻的WKY大鼠和SHR中，用10⁻⁵ mol/L苯那普利拉预处理冠状动脉（每组n = 5）几乎完全消除了对10⁻⁷ mol/L血管紧张素I的收缩反应。所有四组对10⁻⁷ mol/L血管紧张素II的主动壁张力相当，但与对100 mmol/L KCl的收缩反应相比，年轻的SHR（29±3%，n = 9）的反应已高于年轻的WKY大鼠（14±3%，n = 9，P <.05），但在两种品系中年龄对其均无影响。用10⁻⁵ mol/L非肽类血管紧张素II（AT1）受体拮抗剂缬沙坦对年轻的WKY大鼠和SHR冠状动脉进行体外处理（每组n = 3）可完全抑制对10⁻⁷ mol/L血管紧张素II的收缩反应。相反，所有四组大鼠对硝基血管扩张剂硝普钠的非内皮依赖性舒张、对乙酰胆碱的内皮依赖性舒张以及对Nω - 硝基 - L - 精氨酸甲酯的内皮依赖性收缩相当。
总之，在大鼠冠状动脉中，对内皮素 - 1、5 - 羟色胺和KCl的收缩反应随年龄增加，但高血压会使其降低。相反，L - 精氨酸/一氧化氮途径不受影响。仅在SHR中，对血管紧张素I的收缩反应随高血压持续时间的增加而显著增加。尽管SHR冠状动脉的总体收缩反应降低，但对血管紧张素II的收缩反应得以维持。因此，衰老和高血压对大鼠冠状动脉对血管收缩激动剂的收缩反应影响不同。
