Long-term captopril treatment. Angiotensin II receptors and responses.
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 ng) and subcutaneous (100 micrograms/kg) administration of Ang I and II were attenuated in captopril-treated SHR in 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 II, as determined in isolated, artificially perfused kidneys, was elevated. Threshold and ED50 values for Ang II were significantly lower in captopril-treated SHR than in controls. Ang II receptor binding in aortic smooth muscle cells prepared from captopril-treated SHR was also significantly greater than in cells from controls. Thus, lifetime treatment with captopril induced alterations in the renin angiotensin systems in the periphery and brain that were manifested by changes in receptor binding and responsiveness to Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)
Wilson
K M
KM
Department of Physiology and Biophysics, University of Alabama, Birmingham 35294.
Magargal
W
W
Berecek
K H
KH
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D002216:Captopril / Q000627:therapeutic use*; D004327:Drinking Behavior / Q000187:drug effects; D005260:Female; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011945:Receptors, Angiotensin / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013997:Time Factors
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D002216:Captopril