The effects of candesartan on vascular responses to angiotensin II and norepinephrine in normal volunteers.
The effects of chronic administration of candesartan, 16 mg once-daily, to normal volunteers on cardiovascular responses to angiotensin II (Ang II) and norepinephrine (NE) were examined. Fifteen healthy, non-smoking volunteers participated in a randomised, double-blind crossover study of two weeks of candesartan therapy, compared with two weeks of placebo. Blood pressure (BP) responses were measured to increasing infusion rates of intravenous Ang II and NE, along with forearm blood flow (FBF) responses into intra-brachial arterial Ang II, 2 and 24 hours after the last dose of candesartan or placebo. FBF responses to intra-brachial arterial NE were recorded approximately 2 hours following the final dose. Systolic and diastolic BP responses to intravenous infusions of Ang II during candesartan treatment were completely suppressed and significantly lower than during placebo treatment, 2 hours (candesartan 96+/-10/55+/-8 mmHg; placebo 105+/-5/64+/-8 mmHg) and 24 hours (candesartan 94+/-8/54+/-8 mmHg; placebo 103+/-7/64+/-7 mmHg) following the last dose. In contrast, FBF responses to intra-brachial arterial Ang II were significantly suppressed by candesartan compared with placebo in a subgroup of subjects 2 hours following the last dose (n=9), but not 24 hours after the last dose (n=8). FBF responses to NE were also suppressed by candesartan treatment 2 hours following the last dose, while BP responses to intravenous NE were unaltered. Chronic candesartan therapy, 16 mg once-daily effectively suppresses pressor responses to Ang II over the duration of the dosing interval.
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Department of Clinical Pharmacology, St. George Hospital, UNSW, Kogarah, NSW 2210, Australia.
Phoon
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Howes
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D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects*; D001916:Brachial Artery; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C081643:candesartan; D009638:Norepinephrine