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Abstract

We examine whether irbesartan (IRB) and IRB + hydrochlorotiazide (HCTZ) can reverse the non-dipper circadian rhythm of BP to a dipper pattern in salt-sensitive hypertensives (SS-HTs) submitted to a high sodium loading. In a double blind, cross-over study 12 black SS-HTs (7 male, 35-58 years) were kept on a high-sodium diet (300 mmol sodium/d) for 10 weeks (wks). A placebo (PL1) was given during the first 2 wks followed by 2 wks on IRB 150 mg/d (IRB150). Thereafter patients were randomized to follow in a cross-over way either a regimen of a) IRB 300 mg/d (2 wks) followed by placebo (2wks) and IRB 150mg + HCTZ 12.5mg (2wks) or b) IRB 150mg + HCTZ 12.5mg (2wks) followed by placebo (2wks) and IRB 300 mg/d (2 wks). On the last day of PL and IRB150, IRB300 and IRB+HCTZ treatments, 24-h BP was measured and urinary 24h excretion of sodium (UV-Na, mmol/24h). On PL1 ambulatory mean arterial pressure (MAP) was 112±2 (24h), 112±2 (daytime), and 111±2 mmHg (nighttime) showing a clear circadian non-dipper profile. Versus PL, IRB150 reduced MAP by 4.2±1.1 (24h), 2.6±0.8 (daytime) and 6.0±1.3 mmHg (nighttime) (p<0.05 v PL); v PL, IRB300 reduced MAP by 7.8±1.4 (24h), 3.9±1.1 (daytime) and 11.8±2.1 mmHg (nighttime) (all p<0.02 v PL); v PL, IRB+HCTZ reduced MAP by 9.5±1.3 (24h), 8.0±1.2 (daytime) and 11.9±2.3 mmHg (nighttime) (all p<0.02 v PL). Nighttime/daytime MAP fall was of 0.7% on PL, of 3.5% (IRB 150), of 7.0% (IRB 300) and of 5.3% (IRB150+HCTZ). Versus PL, both IR150 and IRB300 reduced urinary sodium excretion (24h) by 14 and 21% respectively whereas was IRB150+HCTZ increased it by 8%. Although IRB300 and IRB150 +HCTZ similarly reduced 24h BP (better than IRB150), IRB dose-dependently reduced BP predominantly during nighttime, thereby reversing the BP non-dipper profile observed during PL despite no increase of sodium excretion. Thus IRB can restore the blunting of nightime BP fall of SS-HT under HS diet. Increment of Na excretion is not needed for this effect. Blunting of nightime BP fall in SS-HT on HS may be related to a defficient suppression of renin angiotensin system during nighttime.

Salt sensitive hypertension, Non-dipper, Therapy
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© American Journal of Hypertension, Ltd. 2001
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