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Abstract

Rapid reversal of angiotensin I-induced contractions in rat carotid arteries after acute and chronic treatment with the angiotensin-converting enzyme inhibitor, 3-[(5-amino-1-carboxy-1S-pentyl)amino]2,3,4,5-tetrahydro-2-oxo- 3S-1H-1-benzazepena-1-acetic acid (CGS 16617).

G B Weiss, B Sturm and N R Levens
Journal of Pharmacology and Experimental Therapeutics December 1993, 267 (3) 1407-1413;
G B Weiss
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B Sturm
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N R Levens
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Abstract

The purpose of these experiments was to determine whether, in carotid arteries obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) a correlation exists between access of the angiotensin-converting enzyme (ACE) inhibitor, 3-[(5-amino-1-carboxy-1S-pentyl)amino]2,3,4,5-tetrahydro-2-oxo-3S- 1H-benzazepena-1-acetic acid (CGS 16617), to tissue sites and the corresponding responsiveness of these tissues to the contractile effect of angiotensin I (ANG I). In carotid arteries isolated from SHR and WKY, the magnitude of [14C]CGS 16617 uptake was slightly greater than the [14C]sucrose uptake (the extracellular space), and the percentages of [14C]CGS 16617 and [14C]sucrose in fast and slow desaturation components were similar. Addition of high concentrations of nonradioactive CGS 16617 (10(-5)M during uptakes or washouts of [14C]CGS 16617 did not change uptake amounts or efflux rates. The dose-response curves of contractions obtained with ANG I or ANG II as well as the dose-dependent inhibition of ANG I-induced responses in the presence of CGS 16617 were similar for carotids taken from both WKY and SHR. Responses to ANG I were restored as early as 5 min after incubation solutions containing inhibitory concentrations of CGS 16617 were removed. Similarly, normal responsiveness to the contractile effects of ANG I were observed with carotid arteries removed from SHR with decreased blood pressure and plasma ACE activity after 5 weeks exposure to CGS 16617. In contrast, however, responses to norepinephrine were decreased in carotid arteries obtained from CGS 16617-treated SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 267, Issue 3
1 Dec 1993
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Abstract

Rapid reversal of angiotensin I-induced contractions in rat carotid arteries after acute and chronic treatment with the angiotensin-converting enzyme inhibitor, 3-[(5-amino-1-carboxy-1S-pentyl)amino]2,3,4,5-tetrahydro-2-oxo- 3S-1H-1-benzazepena-1-acetic acid (CGS 16617).

G B Weiss, B Sturm and N R Levens
Journal of Pharmacology and Experimental Therapeutics December 1, 1993, 267 (3) 1407-1413;

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Abstract

Rapid reversal of angiotensin I-induced contractions in rat carotid arteries after acute and chronic treatment with the angiotensin-converting enzyme inhibitor, 3-[(5-amino-1-carboxy-1S-pentyl)amino]2,3,4,5-tetrahydro-2-oxo- 3S-1H-1-benzazepena-1-acetic acid (CGS 16617).

G B Weiss, B Sturm and N R Levens
Journal of Pharmacology and Experimental Therapeutics December 1, 1993, 267 (3) 1407-1413;
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