Autopotentiation of pressor responses by subpressor angiotensin II in rats.
The mechanisms whereby the continuous administration of initially subpressor doses of angiotensin II (ANG II) leads to pressor hyperresponsiveness and gradual development of hypertension were investigated. Male Sprague-Dawley rats (350 to 400 g) were given ANG II intraperitoneally, 200 ng/kg/min, for 24 h, 7 to 10 days, or 6 weeks. Vehicle-infused rats were controls. Pressor responses to incremental doses of ANG II, norepinephrine (NE), and serotonin were measured in chloralose-anesthetized rats, before and after neurohumoral blockade, and the main findings were confirmed in awake, free-moving rats with implanted catheters. Pressure responses to ANG II and NE were also measured in the isolated, pump-perfused mesenteric circulation of rats after 7 to 10 days of ANG II or sham infusion. Compared with control rats, there were no hemodynamic changes in ANG II-treated rats at 24 h. After 7 to 10 days of ANG II treatment, tail systolic blood pressure rose by 13 mm Hg (P < .01) and pressor responses to ANG II (P < .01) but not to NE or serotonin were increased. Pressor hyperresponsiveness was due in part to potentiation of vascular responses because pressure responses to ANG II (P < .002) but not to NE were also increased in the mesenteric circulation of ANG II-treated rats. By 6 weeks, mild hypertension was well established in ANG II-treated rats and pressor responses were increased to both ANG II (P < .05) and NE (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Abraham
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Department of Medicine, Veterans Affairs Medical Center, Minneapolis, MN 55417.
Simon
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G
D000595:Amino Acid Sequence; D000758:Anesthesia; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002698:Chloralose; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D008297:Male; D008969:Molecular Sequence Data; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012701:Serotonin / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000187:drug effects; D014667:Vasopressins / Q000097:blood
D014667:Vasopressins; D000804:Angiotensin II; D002698:Chloralose; D012701:Serotonin; D012083:Renin; D009638:Norepinephrine