Endothelial function during stimulation of renin-angiotensin system by low-sodium diet in humans.
We examined whether physiological stimulation of the endogenous renin-angiotensin system results in impaired endothelium-dependent vasodilatation in forearm resistance vessels of healthy subjects and whether this impairment can be prevented by angiotensin II type 1 receptor blockade. A low-sodium diet was administered to 27 volunteers who were randomized to concomitant treatment with losartan (100 mg once daily) or matched placebo in a double-blind fashion. Forearm blood flow was assessed by venous occlusion plethysmography at baseline and after 5 days. Endothelium-dependent and -independent vasodilation was assessed by intra-arterial infusion of methacholine and verapamil, respectively. The low-sodium diet resulted in significantly decreased urine sodium excretion (placebo: 146 +/- 64 vs. 10 +/- 9 meq/24 h, P < 0.001; losartan: 141 +/- 56 vs. 14 +/- 14 meq/24 h, P < 0.001) and increased plasma renin activity (placebo: 1.0 +/- 0.5 vs. 5.0 +/- 2.5 ng x ml(-1) x h(-1), P < 0.001; losartan: 3.8 +/- 7.2 vs. 19.1 +/- 11.2 ng x ml(-1) x h(-1), P = 0.006) in both the losartan and placebo groups. With the baseline study as the reference, the diet intervention was not associated with any significant change in endothelium-dependent vasodilation to methacholine in either the placebo (P = 0.74) or losartan (P = 0.40) group. We conclude that short-term physiological stimulation of the renin-angiotensin system does not cause clinically significant endothelial dysfunction. Losartan did not influence endothelium-dependent vasodilation in humans with a stimulated renin-angiotensin system.
Omland
T
T
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Johnson
W
W
Gordon
M B
MB
Creager
M A
MA
D000328:Adult; D000804:Angiotensin II / Q000378:metabolism; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism; D010277:Parasympathomimetics / Q000008:administration & dosage; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary / Q000008:administration & dosage*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
D000959:Antihypertensive Agents; D010277:Parasympathomimetics; D012982:Sodium, Dietary; D016210:Methacholine Chloride; D000804:Angiotensin II; D009569:Nitric Oxide; D012964:Sodium; D019808:Losartan