Zhang Jin, Hamlyn John M, Karashima Eiji, Raina Hema, Mauban Joseph R H, Izuka Michelle, Berra-Romani Roberto, Zulian Alessandra, Wier W Gil, Blaustein Mordecai P
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Am J Physiol Heart Circ Physiol. 2009 Sep;297(3):H1140-50. doi: 10.1152/ajpheart.00436.2009. Epub 2009 Jul 17.
Prolonged ouabain administration to normal rats causes sustained blood pressure (BP) elevation. This ouabain-induced hypertension (OH) has been attributed, in part, to the narrowing of third-order resistance arteries (approximately 320 microm internal diameter) as a result of collagen deposition in the artery media. Here we describe the structural and functional properties of fourth-order mesenteric small arteries from control and OH rats, including the effect of low-dose ouabain on myogenic tone in these arteries. Systolic BP in OH rats was 138 +/- 3 versus 124 +/- 4 mmHg in controls (P < 0.01). Pressurized (70 mmHg) control and OH arteries, with only a single layer of myocytes, both had approximately 165-microm internal diameters and approximately 20-microm wall thicknesses. Even after fixation, despite vasoconstriction, the diameters and wall thicknesses did not differ between control and OH fourth-order arteries, whereas in third-order arteries, both parameters were significantly smaller in OH than in controls. Myogenic reactivity was significantly augmented in OH fourth-order arteries. Nevertheless, phenylephrine- (1 microM) and high K(+)-induced vasoconstrictions and acetylcholine-induced vasodilation were comparable in control and OH arteries. Vasoconstrictions induced by 5 microM phenylephrine and by 10 mM caffeine in Ca(2+)-free media indicated that releasable sarcoplasmic reticulum Ca(2+) stores were normal in OH arteries. Importantly, 100 nM ouabain constricted both control and OH arteries by approximately 26 microm, indicating that this response was not downregulated in OH rats. This maximal ouabain-induced constriction corresponds to a approximately 90% increase in resistance to flow in these small arteries; thus ouabain at EC(50) of approximately 0.66 nM should raise resistance by approximately 35%. We conclude that dynamic constriction in response to circulating nanomolar ouabain in small arteries likely makes a major contribution to the increased vascular tone and BP in OH rats.
对正常大鼠长期给予哇巴因会导致血压持续升高。这种哇巴因诱导的高血压（OH）部分归因于三级阻力动脉（内径约320微米）因动脉中膜胶原蛋白沉积而变窄。在此，我们描述了对照大鼠和OH大鼠肠系膜四级小动脉的结构和功能特性，包括低剂量哇巴因对这些动脉肌源性张力的影响。OH大鼠的收缩压为138±3 mmHg，而对照大鼠为124±4 mmHg（P<0.01）。在70 mmHg压力下，对照动脉和OH动脉都只有单层肌细胞，内径约为165微米，壁厚约为20微米。即使在固定后，尽管血管收缩，对照四级动脉和OH四级动脉的直径和壁厚并无差异，而在三级动脉中，OH动脉的这两个参数均显著小于对照动脉。OH四级动脉的肌源性反应性显著增强。然而，去氧肾上腺素（1 microM）和高钾诱导的血管收缩以及乙酰胆碱诱导的血管舒张在对照动脉和OH动脉中相当。在无钙培养基中，5 microM去氧肾上腺素和10 mM咖啡因诱导的血管收缩表明，OH动脉中可释放的肌浆网钙储备正常。重要的是，100 nM哇巴因使对照动脉和OH动脉均收缩约26微米，表明这种反应在OH大鼠中并未下调至基础水平。这种最大哇巴因诱导的收缩相当于这些小动脉血流阻力增加约90%；因此，在约0.66 nM的半数有效浓度（EC50）下，哇巴因应使阻力增加约35%。我们得出结论，小动脉对循环中纳摩尔浓度哇巴因的动态收缩可能对OH大鼠血管张力和血压升高起主要作用。
