Charpie J R, Charpie P M, Goud C, Pitt B, Webb R C
Department of Pediatrics, University of Michigan Medical School, Ann Arbor, USA.
Blood Press. 1997 Mar;6(2):117-24. doi: 10.3109/08037059709061810.
Long-term inhibition of nitric oxide synthase (NOS) by substituted arginine analogues has previously been shown to induce systemic hypertension in several animal species; however, the precise mechanisms for the elevated blood pressure remain unclear. We hypothesized that a portion of the hypertensive response to arginine analogues was due to direct inhibition of endothelial NOS and resultant functional alterations in the vasculature that contribute to elevated systemic resistance. Adult Sprague-Dawley rats were treated for 2 weeks with an arginine analogue, N omega Nitro-L-arginine (L-NNA), alone or in combination with the angiotensin converting enzyme (ACE) inhibitor quinapril. Next, thoracic aortas were removed, cut into rings and suspended in isolated tissue baths for measurement of contractile force in response to vasoactive drugs. Our results showed that oral L-NNA treatment significantly elevated systolic blood pressure in rats that was completely prevented by quinapril. Furthermore, L-NNA treatment increased endothelium-dependent and -independent contractility and attenuated endothelium-dependent vasodilation in the thoracic aorta. These functional alterations were also attenuated by quinapril treatment. Therefore, long-term L-NNA-induced hypertension in rats is associated with enhanced vascular reactivity due both to direct inhibition of endothelial NOS and to stimulation of the renin-angiotensin system.
此前已表明，用取代精氨酸类似物长期抑制一氧化氮合酶（NOS）会在几种动物物种中诱发全身性高血压；然而，血压升高的确切机制仍不清楚。我们推测，对精氨酸类似物的部分高血压反应是由于直接抑制内皮型NOS以及血管系统中由此产生的功能改变，这些改变导致全身阻力升高。成年Sprague-Dawley大鼠用精氨酸类似物Nω-硝基-L-精氨酸（L-NNA）单独或与血管紧张素转换酶（ACE）抑制剂喹那普利联合治疗2周。接下来，取出胸主动脉，切成环并悬挂在离体组织浴中，以测量对血管活性药物的收缩力。我们的结果表明，口服L-NNA治疗可显著提高大鼠的收缩压，而喹那普利可完全预防这种情况。此外，L-NNA治疗增加了胸主动脉中内皮依赖性和非依赖性收缩性，并减弱了内皮依赖性血管舒张。喹那普利治疗也减弱了这些功能改变。因此，长期L-NNA诱导的大鼠高血压与血管反应性增强有关，这既是由于直接抑制内皮型NOS，也是由于刺激肾素-血管紧张素系统。
