Wu J N, Tsai S Y, Hsieh W Y
Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, ROC.
Chin J Physiol. 2001 Jun 30;44(2):59-65.
Previously, we had found that inhibition of the renin-angiotensin system in the early lifespan of spontaneously hypertensive rat could prevent the development of hypertension in this animal model. In the present study we evaluated the responses of blood pressure and renal function to intracerebroventricular administration of angiotensin II in long-term captopril-treated spontaneously hypertensive rats. Spontaneously hypertensive rats had been mated and their pups were treated with captopril through drinking water after birth. Age-matched Wistar-Kyoto and spontaneously hypertensive rats drinking tap water were used as control groups. At 4 months of age, the basal mean arterial blood pressure of captopril-treated hypertensive rats was the lowest among those of controlled hypertensive and normotensive rats (98+/-5 vs. 160+/-4 and 126+/-4 mmHg, respectively). Intravenous administration of angiotensin II caused similar increments of blood pressure in all rat groups. However, intracerebroventricular administration of angiotensin II to captopril-treated hypertensive rats induced a significantly less increase of arterial blood pressure in comparison with other groups. The sensitivity of baroreflex in captopril-treated hypertensive rats was also the lowest among all rat groups. The basal urine flow, sodium and potassium excretion rates, and osmolar clearance of captopril-treated hypertensive rats were significantly higher than those of controlled hypertensive rats. Intracerebroventricular infusion of angiotensin II caused significant increases in urine flow, electrolytes excretion, osmolar clearance, and free water reabsorption rate of both normotensive and controlled hypertensive rats. However, the same angiotensin II treatment did not change any of the renal excretion indices in captopril-treated hypertensive rats. Our results suggest that lifetime captopril treatment can decrease the activity of the renin-angiotensin system in the brain of hypertensive animals, which caused increases in basal urine flow and excretion of electrolytes and enhanced the sensitivity of baroreflex. It is likely that changes in the renal and baroreflex functions underlie the prevention of hypertension elicited by long-term captopril treatment.
此前，我们发现，在自发性高血压大鼠生命早期抑制肾素 - 血管紧张素系统可预防该动物模型中高血压的发展。在本研究中，我们评估了长期接受卡托普利治疗的自发性高血压大鼠脑室内注射血管紧张素II后血压和肾功能的反应。自发性高血压大鼠进行交配，其幼崽出生后通过饮水给予卡托普利治疗。饮用自来水的年龄匹配的Wistar - Kyoto大鼠和自发性高血压大鼠作为对照组。在4个月龄时，接受卡托普利治疗的高血压大鼠的基础平均动脉血压在对照高血压大鼠和正常血压大鼠中是最低的（分别为98±5 mmHg与160±4 mmHg和126±4 mmHg）。静脉注射血管紧张素II在所有大鼠组中引起相似的血压升高。然而，与其他组相比，对接受卡托普利治疗的高血压大鼠脑室内注射血管紧张素II引起的动脉血压升高明显较小。在所有大鼠组中，接受卡托普利治疗的高血压大鼠的压力感受性反射敏感性也是最低的。接受卡托普利治疗的高血压大鼠的基础尿流量、钠和钾排泄率以及渗透清除率显著高于对照高血压大鼠。脑室内注入血管紧张素II导致正常血压大鼠和对照高血压大鼠的尿流量、电解质排泄、渗透清除率和自由水重吸收率显著增加。然而，相同的血管紧张素II处理并未改变接受卡托普利治疗的高血压大鼠的任何肾脏排泄指标。我们的结果表明，终生卡托普利治疗可降低高血压动物脑中肾素 - 血管紧张素系统的活性，这导致基础尿流量增加和电解质排泄增加，并增强了压力感受性反射的敏感性。长期卡托普利治疗预防高血压的机制可能是肾脏和压力感受性反射功能的改变。
