Maeso R, Rodrigo E, Muñoz-García R, Navarro-Cid J, Ruilope L M, Cachofeiro V, Lahera V
Department of Physiology, School of Medicine, Complutense University, Madrid, Spain.
J Hypertens. 1998 May;16(5):665-72. doi: 10.1097/00004872-199816050-00014.
To evaluate the effects of prolonged treatment with losartan on endothelium-dependent and endothelium-independent relaxations of aortic rings from adult and senescent spontaneously hypertensive rats, and to clarify whether these effects were due to specific mechanisms of the drug or a consequence of its blood-pressure-lowering action.
Adult (aged 5 months) and senescent (aged 20 months) male spontaneously hypertensive rats were treated for 12 consecutive weeks with 10 mg/kg per day losartan. Systolic blood pressure and plasma concentration of nitrates were evaluated. We studied endothelium-dependent and endothelium-independent relaxations and response to angiotensin II of aortic rings from rats of each group. The direct effects of angiotensin II type 1 receptor antagonism on vascular reactivity of aortic rings from untreated adult and senescent rats that had been incubated beforehand with losartan were also studied.
Losartan treatment comparably reduced blood pressure and increased plasma concentration of nitrates in rats of both age groups. Responses to acetylcholine and sodium nitroprusside were lower for rings from senescent than they were for rings from adult rats. Constrictor responses to angiotensin II were higher for rings from senescent than they were for rings from adult rats. Treatment with losartan increased the magnitude of relaxations in response to acetylcholine for rings from rats in both groups, but increased the magnitude of relaxations in response to nitroprusside only for rings from senescent spontaneously hypertensive rats. Incubation beforehand of aortic rings from untreated rats with losartan enhanced magnitude of relaxations in response both to acetylcholine and to nitroprusside only for rings from senescent spontaneously hypertensive rats.
The consequences of aging for endothelium-dependent and endothelium-independent relaxations of rings from spontaneously hypertensive rats are ameliorated by losartan treatment, suggesting that angiotensin II plays a role via type 1 receptors. The effects of losartan on senescent spontaneously hypertensive rats were due not only to its blood-pressure-lowering action but also to the blockade of specific mechanisms derived from angiotensin II type 1 receptor antagonism, which might involve an increase in availability of NO.
评估氯沙坦长期治疗对成年和老年自发性高血压大鼠主动脉环内皮依赖性和非内皮依赖性舒张的影响，并阐明这些影响是由于药物的特定机制还是其降压作用的结果。
成年（5月龄）和老年（20月龄）雄性自发性高血压大鼠每天用10mg/kg氯沙坦连续治疗12周。评估收缩压和血浆硝酸盐浓度。我们研究了每组大鼠主动脉环的内皮依赖性和非内皮依赖性舒张以及对血管紧张素II的反应。还研究了1型血管紧张素II受体拮抗剂对预先用氯沙坦孵育的未治疗成年和老年大鼠主动脉环血管反应性的直接影响。
氯沙坦治疗可同等程度降低两个年龄组大鼠的血压并增加血浆硝酸盐浓度。老年大鼠主动脉环对乙酰胆碱和硝普钠的反应低于成年大鼠主动脉环。老年大鼠主动脉环对血管紧张素II的收缩反应高于成年大鼠主动脉环。氯沙坦治疗增加了两组大鼠主动脉环对乙酰胆碱的舒张幅度，但仅增加了老年自发性高血压大鼠主动脉环对硝普钠的舒张幅度。预先用氯沙坦孵育未治疗大鼠的主动脉环，仅增加了老年自发性高血压大鼠主动脉环对乙酰胆碱和硝普钠的舒张幅度。
氯沙坦治疗可改善衰老对自发性高血压大鼠主动脉环内皮依赖性和非内皮依赖性舒张的影响，提示血管紧张素II通过1型受体发挥作用。氯沙坦对老年自发性高血压大鼠的作用不仅归因于其降压作用，还归因于对源自1型血管紧张素II受体拮抗剂的特定机制的阻断，这可能涉及一氧化氮可用性的增加。
