Efficacy of carvedilol in reversing hypertension induced by chronic intermittent hypoxia in rats.
Animal models of chronic intermittent hypoxia (CIH) mimic the hypertension observed in patients with obstructive sleep apnoea. Antihypertensive drugs were applied to these animal models to address the physiological mechanism but not to revert established hypertension. We aimed to investigate the efficacy of carvedilol (CVDL), an unselective beta-blocker that exhibits intrinsic anti-α1-adrenergic and antioxidant activities in a rat model of CIH-induced hypertension. The variability of CVDL enantiomers in plasma concentrations was also evaluated. Wistar rats with indwelling blood pressure telemeters were exposed during their sleep period to 5.6 CIH cycles/h, 10.5 h/day, for 60 days. CVDL was administered by gavage beginning on Day 36 of the CIH period and was continued for 25 days. R-(+)-CVDL and S-(-)-CVDL plasma concentrations were monitored by HPLC. CIH significantly increased diastolic and systolic blood pressure by 25.7 and 21.6 mm Hg respectively, while no effect was observed on the heart rate (HR). CVDL administration at 10, 30 and 50 mg/kg/day promoted a significant reduction in HR but did not affect arterial pressure. The S/(R+S) ratio of CVDL enantiomers was lower in rats exposed to CIH. The blockade of the sympathetic nervous system together with the putative pleiotropic effects of CVDL did not alter the CIH-induced hypertension. Although CIH induced pharmacokinetic changes in the R/(R+S) ratio, these effects do not appear to be responsible for the inability of CVDL to reverse this particular type of hypertension.
CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal. Electronic address: lucilia.diogo@fcm.unl.pt.
Lucília N
LN
Diogo
CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal.
Sofia A
SA
Pereira
CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal.
Ana R
AR
Nunes
CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal.
Ricardo A
RA
Afonso
NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal.
Ana I
AI
Santos
CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal.
Emília C
EC
Monteiro
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D002908:Chronic Disease; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D011412:Propanolamines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol
Antihypertensive drugs; Beta-blockers; Carvedilol; Chronic intermittent hypoxia; Telemetry