Panza J A, Casino P R, Kilcoyne C M, Quyyumi A A
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Am Coll Cardiol. 1994 Jun;23(7):1610-6. doi: 10.1016/0735-1097(94)90664-5.
The purpose of this study was to determine whether the impaired endothelium-dependent vasodilation of hypertensive patients is related to a specific defect of the muscarinic receptor or to a broader abnormality of the vascular endothelium.
Patients with essential hypertension have abnormal endothelium-dependent vasodilator response to acetylcholine. However, whether this results from an isolated dysfunction of the endothelial cell muscarinic receptor is unknown.
The responses of the forearm vasculature to acetylcholine and substance P (endothelium-dependent agents acting on different receptors) and to sodium nitroprusside (a direct dilator of vascular smooth muscle) were studied in eight hypertensive patients (six men, two women; mean age [+/- SD] 50 +/- 12 years) and eight normal control subjects (four men, four women; mean age 49 +/- 9 years). To determine the nitric oxide contribution to substance P-induced vasodilation, the vascular responses to substance P were also measured after inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine. Drugs were infused into the brachial artery, and forearm blood flow was measured by strain gauge plethysmography.
The response to acetylcholine was significantly blunted in hypertensive patients (highest blood flow [mean +/- SD] 8.4 +/- 4 vs. 13.8 +/- 4 ml/min per 100 ml in control subjects, p < 0.03). Similarly, the vasodilator effect of substance P was significantly reduced in hypertensive patients (highest blood flow [mean +/- SD] 8.8 +/- 4 vs. 13.9 +/- 4 ml/min per 100 ml in control subjects, p < 0.03). A significant correlation was found between the maximal blood flow with acetylcholine and that with substance P (r = 0.68, p < 0.004). The vasodilator response to sodium nitroprusside was similar in patients and control subjects. The nitric oxide contribution to substance P-induced vasodilation was reduced in hypertensive patients, such that the responses to substance P measured during infusion of NG-monomethyl-L-arginine were not significantly different between the two groups.
These findings indicate that the endothelial abnormality of patients with essential hypertension is not restricted to the muscarinic cell receptor.
本研究旨在确定高血压患者内皮依赖性血管舒张功能受损是否与毒蕈碱受体的特定缺陷或血管内皮的更广泛异常有关。
原发性高血压患者对乙酰胆碱的内皮依赖性血管舒张反应异常。然而，这是否源于内皮细胞毒蕈碱受体的孤立功能障碍尚不清楚。
研究了8例高血压患者（6例男性，2例女性；平均年龄[±标准差]50±12岁）和8例正常对照者（4例男性，4例女性；平均年龄49±9岁）前臂血管对乙酰胆碱和P物质（作用于不同受体的内皮依赖性药物）以及硝普钠（血管平滑肌的直接扩张剂）的反应。为了确定一氧化氮对P物质诱导的血管舒张的作用，在用NG-单甲基-L-精氨酸抑制一氧化氮合成后，也测量了血管对P物质的反应。将药物注入肱动脉，并用应变片体积描记法测量前臂血流量。
高血压患者对乙酰胆碱的反应明显减弱（最高血流量[平均±标准差]为8.4±4，而对照组为每100ml 13.8±4ml/min，p<0.03）。同样，高血压患者中P物质的血管舒张作用也显著降低（最高血流量[平均±标准差]为8.8±4，而对照组为每100ml 13.9±4ml/min，p<0.03）。发现乙酰胆碱的最大血流量与P物质的最大血流量之间存在显著相关性（r=0.68，p<0.004）。患者和对照者对硝普钠的血管舒张反应相似。高血压患者中一氧化氮对P物质诱导的血管舒张的作用降低，因此在注入NG-单甲基-L-精氨酸期间测量的两组对P物质的反应无显著差异。
这些发现表明，原发性高血压患者的内皮异常并不局限于毒蕈碱细胞受体。
