Long-term Captopril Treatment Angiotensin II Receptors and Responses

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 11; no. 2, Part 2 Suppl I; pp. I-148 - I-152
• Main Authors: WILSON, KAREN M, MAGARGAL, WELLS, BERECEK, KATHLEEN H
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.02.1988
• Subjects: Angiotensin II - metabolism; Animals; Captopril - therapeutic use; Drinking Behavior - drug effects; Female; Hypertension - drug therapy; Male; Muscle, Smooth, Vascular - drug effects; Rats; Rats, Inbred SHR; Receptors, Angiotensin - drug effects; Renin-Angiotensin System - drug effects; Time Factors
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.11.2_pt_2.i148

The purpose of this study was to elucidate the mechanism of the antihypertensive effect of the angiotensin I (Ang I) converting enzyme inhibitor captopril in spontaneously hypertensive rats (SHR). Drinking responses, peripheral vascular reactivity, and angiotensin II (Ang II) receptor binding in both the brain and vascular smooth muscle were examined in control and captopril-treated SHR. Pregnant and nursing dams were treated with oral captopril (100 mg/kg). After weaning, offspring were maintained on captopril (50 mg/kg). The average systolic pressures after 21 weeks of captopril treatment were 122 ± 3 mm Hg (male) and 118 ± 4 mm Hg (female) as compared with 169 ± 4 mm Hg (male) and 162 ± 2 mm Hg (female) in age-matched controls. Drinking responses to intracerebroventricular (10 ngj and subcutaneous (100 μg/kg) administration of Ang I and II were attenuated hi captopril-treated SHR hi comparison to control SHR. Ang II receptor binding in the hypothalamus, thalamus, and septum of captopril-treated SHR was also significantly reduced. In contrast to a depressed angiotensinergic system in the brain, peripheral vascular reactivity to Ang H, as determined in isolated, artificially perfused kidneys, was elevated. Threshold and EDn values for Ang H were significantly lower in captopril-treated SHR than hi controls. Ang II receptor binding hi aortic smooth muscle cells prepared from captopril-treated SHR was also significantly greater than hi cells from controls. Thus, lifetime treatment with captopril induced alterations in the reninangiotensin systems in the periphery and brain that were manifested by changes in receptor binding and responsiveness to Ang II. However, the effects of treatment were not the same on vascular and central Ang II receptors, suggesting differential regulation.