Ernesto L Schiffrin1, Jeong Bae Park, Qian Pu. 1. Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montréal, University of Montréal, 110 Pine Avenue West, Montréal, Québec, Canada H2W 1R7. schiffe@ircm.qc.ca
Abstract
BACKGROUND: Treatment of essential hypertensive patients with anAT1 angiotensin receptor antagonist has previously resulted in correction of resistance artery structure and endothelial function, whereas in a parallel group treated with the beta-blocker atenolol there was no improvement of altered vascular structure and function. To test the hypothesis that patients previously treated with atenolol could present improvement of vascular structure and endothelial function if they were subjected to blockade of the renin-angiotensin system, we crossed over hypertensive patients that had been randomized to treatment with the beta-blocker atenolol to treatment with the AT1 antagonist irbesartan, and studied small artery structure and endothelial function before and after treatment. METHODS:Eleven essential hypertensive patients (51 +/- 2 years, range 38-65; 75% male) that had previously been randomized to treatment with atenolol and treated for 1 year with good blood pressure control, were crossed over to treatment with the AT1 antagonist irbesartan for 1 year. Small resistance arteries were dissected from gluteal subcutaneous biopsies that were performed before and after 1 year of treatment. The structure and endothelial function of the resistance arteries were studied on a pressurized myograph. RESULTS:Blood pressure control (129 +/- 3.3/85 +/- 1.8 mmHg) was identical to that achieved previously with atenolol (131 +/- 3.3/84 +/- 1.1 mmHg). Following 1 year of treatment, the arterial media width to lumen ratio (M/L) of resistance arteries (lumen diameter, 150-350 microm), which had remained unchanged under atenolol treatment, decreased from 8.44 +/- 0.45% when patients were on atenolol, to 6.46 +/- 0.30%, P < 0.01, when patients received irbesartan. Maximal acetylcholine-induced endothelium-dependent relaxation was 81.1 +/- 4.1% when patients were on atenolol, unchanged from before starting treatment with the beta-blocker, and was normalized by irbesartan (to 94.8 +/- 2.0%, P < 0.01). CONCLUSION: Crossing over essential hypertensive patients with well-controlled blood pressure from the beta-blocker atenolol to the AT1 receptor antagonist irbesartan resulted in correction of previously persistently altered vascular structure and endothelial function, suggesting a structural and endothelial vascular protective effect of antihypertensive treatment with the AT1 receptor antagonist.
RCT Entities:
BACKGROUND: Treatment of essential hypertensivepatients with an AT1 angiotensin receptor antagonist has previously resulted in correction of resistance artery structure and endothelial function, whereas in a parallel group treated with the beta-blocker atenolol there was no improvement of altered vascular structure and function. To test the hypothesis that patients previously treated with atenolol could present improvement of vascular structure and endothelial function if they were subjected to blockade of the renin-angiotensin system, we crossed over hypertensivepatients that had been randomized to treatment with the beta-blocker atenolol to treatment with the AT1 antagonist irbesartan, and studied small artery structure and endothelial function before and after treatment. METHODS: Eleven essential hypertensivepatients (51 +/- 2 years, range 38-65; 75% male) that had previously been randomized to treatment with atenolol and treated for 1 year with good blood pressure control, were crossed over to treatment with the AT1 antagonist irbesartan for 1 year. Small resistance arteries were dissected from gluteal subcutaneous biopsies that were performed before and after 1 year of treatment. The structure and endothelial function of the resistance arteries were studied on a pressurized myograph. RESULTS: Blood pressure control (129 +/- 3.3/85 +/- 1.8 mmHg) was identical to that achieved previously with atenolol (131 +/- 3.3/84 +/- 1.1 mmHg). Following 1 year of treatment, the arterial media width to lumen ratio (M/L) of resistance arteries (lumen diameter, 150-350 microm), which had remained unchanged under atenolol treatment, decreased from 8.44 +/- 0.45% when patients were on atenolol, to 6.46 +/- 0.30%, P < 0.01, when patients received irbesartan. Maximal acetylcholine-induced endothelium-dependent relaxation was 81.1 +/- 4.1% when patients were on atenolol, unchanged from before starting treatment with the beta-blocker, and was normalized by irbesartan (to 94.8 +/- 2.0%, P < 0.01). CONCLUSION: Crossing over essential hypertensivepatients with well-controlled blood pressure from the beta-blocker atenolol to the AT1 receptor antagonist irbesartan resulted in correction of previously persistently altered vascular structure and endothelial function, suggesting a structural and endothelial vascular protective effect of antihypertensive treatment with the AT1 receptor antagonist.
Authors: R Preston Mason; Robert F Jacob; Ruslan Kubant; Adam Jacoby; Febee Louka; J Jose Corbalan; Tadeusz Malinski Journal: Br J Clin Pharmacol Date: 2012-07 Impact factor: 4.335
Authors: Isola A M Brown; Lukas Diederich; Miranda E Good; Leon J DeLalio; Sara A Murphy; Miriam M Cortese-Krott; Jennifer L Hall; Thu H Le; Brant E Isakson Journal: Arterioscler Thromb Vasc Biol Date: 2018-09 Impact factor: 8.311