MacLeod A B, Vasdev S, Smeda J S
Division of Basic Medical Sciences, Memorial University, St John's, Newfoundland, Canada.
Stroke. 1997 Sep;28(9):1821-8; discussion 1829. doi: 10.1161/01.str.28.9.1821.
We tested the hypothesis that the lowering of plasma aldosterone levels contributed to the antistroke effects of captopril treatment in Wistar Kyoto stroke-prone spontaneously hypertensive rats (SHRSP).
The suppression of plasma aldosterone by captopril treatment (50 mg.kg-1.d-1) was prevented by the subcutaneous infusion of aldosterone into captopril-treated SHRSP. We studied the effect this had on blood pressure (BP) and stroke development.
SHRSP fed a Japanese-style diet containing 4% NaCl developed hypertension and a 100% mortality associated with intracerebral hemorrhage by 14 weeks of age. Captopril treatment from 6 weeks of age did not lower the BP but increased survival past 35 weeks of age. Hydralazine treatment (40 to 80 mg/L of drinking water) lowered BP in SHRSP but was less effective than captopril in retarding stroke. Plasma aldosterone levels were elevated with age in SHRSP after 10 weeks and were higher in poststroke versus prestroke SHRSP. Captopril treatment suppressed plasma aldosterone. When we elevated plasma aldosterone in captopril-treated SHRSP to levels between those present in untreated pre- and poststroke SHRSP, the ability of captopril to retard stroke development was negated. The effects of aldosterone were mimicked by deoxycorticosterone (40 mg/kg, SC2 times/wk) but not by dexamethasone (0.1 mg.kg-1.d-1, SC). Spironolactone treatment (20 mg.kg-1.d-1, SC) of SHRSP reduced BP but had little effect on stroke development.
Elevations in plasma aldosterone enhance stroke development within captopril-treated SHRSP through mechanisms that do not involve stimulation of mineralocorticoid receptors or the enhancement of hypertension. The antistroke effects of captopril treatment may be partially mediated through the suppression of plasma aldosterone.
我们检验了以下假设，即降低血浆醛固酮水平有助于卡托普利治疗对易患中风的Wistar Kyoto自发性高血压大鼠（SHRSP）产生抗中风作用。
通过向接受卡托普利治疗的SHRSP皮下输注醛固酮，阻止卡托普利治疗（50mg·kg⁻¹·d⁻¹）对血浆醛固酮的抑制作用。我们研究了这对血压（BP）和中风发展的影响。
喂食含4%氯化钠的日式饮食的SHRSP在14周龄时出现高血压，且100%的死亡率与脑出血相关。从6周龄开始进行卡托普利治疗并未降低血压，但提高了35周龄后的生存率。肼屈嗪治疗（40至80mg/L饮用水）可降低SHRSP的血压，但在延缓中风方面不如卡托普利有效。10周后，SHRSP的血浆醛固酮水平随年龄升高，中风后SHRSP的血浆醛固酮水平高于中风前。卡托普利治疗可抑制血浆醛固酮。当我们将接受卡托普利治疗的SHRSP的血浆醛固酮水平提高到未治疗的中风前和中风后SHRSP之间的水平时，卡托普利延缓中风发展的能力被消除。脱氧皮质酮（40mg/kg，皮下注射，每周2次）可模拟醛固酮的作用，但地塞米松（0.1mg·kg⁻¹·d⁻¹，皮下注射）则不能。螺内酯治疗（20mg·kg⁻¹·d⁻¹，皮下注射）的SHRSP血压降低，但对中风发展影响不大。
血浆醛固酮升高通过不涉及刺激盐皮质激素受体或加重高血压的机制，增强了接受卡托普利治疗的SHRSP的中风发展。卡托普利治疗的抗中风作用可能部分通过抑制血浆醛固酮来介导。
