Effect of crossing over hypertensive patients from a beta-blocker to an angiotensin receptor antagonist on resistance artery structure and on endothelial function.
BACKGROUND
Treatment of essential hypertensive patients 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 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).


CONCLUSIONS
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.
Schiffrin
Ernesto L
EL
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
Park
Jeong Bae
JB
Pu
Qian
Q
D000109:Acetylcholine / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001158:Arteries / Q000187:drug effects*; D001262:Atenolol / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004232:Diuretics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004452:Echocardiography; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000627:therapeutic use; D011945:Receptors, Angiotensin / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use; D013777:Tetrazoles / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D004232:Diuretics; D011945:Receptors, Angiotensin; D049993:Sodium Chloride Symporter Inhibitors; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D009599:Nitroprusside; D001262:Atenolol; D000077405:Irbesartan; D000109:Acetylcholine