Cardiovascular effects of nebivolol in spontaneously hypertensive rats persist after treatment withdrawal.
OBJECTIVE
We observed previously that nebivolol treatment for 2 months reduced cardiovascular lesions in spontaneously hypertensive rats (SHR). Therefore, we investigated whether this beneficial effect is increased with a longer treatment, and its persistence after withdrawal.


METHODS
Male SHR were treated with 8 mg/kg per day of nebivolol (N-SHR) for 6 months. A separate group was also given identical treatment but they were then monitored for a further 3 months after drug withdrawal. SHR and Wistar-Kyoto rats (WKY) receiving vehicle were used as controls. Systolic blood pressure and heart rate were measured using the tail-cuff method. Left ventricular weight/body weight ratio was calculated as the hypertrophy index. Cardiac and vascular fibrosis was evaluated on sections stained with sirious red. Vascular reactivity was evaluated on aortic rings through acetylcholine and sodium nitroprusside responses. The effect of treatment on vascular structure was assessed by lumen diameter, wall thickness and medial cross-sectional area determination.


RESULTS
Blood pressure was reduced in N-SHR. After withdrawal it increased progressively, without reaching the values of the hypertensive controls. Cardiac hypertrophy and collagen content both in heart and aorta were significantly reduced, and these changes persisted after nebivolol suppression. Acetylcholine-induced relaxant response was improved by nebivolol and maintained after withdrawal. Medial thickness and cross-sectional area were significantly reduced in both conductance and resistance arteries, and these effects persisted after withdrawal.


CONCLUSIONS
The nebivolol antihypertensive effect was accompanied by an important reduction of hypertrophy and collagen deposition in both vascular and left ventricle tissue, which was maintained after a long period of therapy withdrawal.
Guerrero
Estela I
EI
Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Spain.
Ardanaz
Noelia
N
Sevilla
María A
MA
Arévalo
Miguel A
MA
Montero
María J
MJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006332:Cardiomegaly / Q000503:physiopathology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects*; D003094:Collagen / Q000032:analysis; D004983:Ethanolamines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000737:chemistry; D000068577:Nebivolol; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors
D000959:Antihypertensive Agents; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D009599:Nitroprusside; D003094:Collagen; D000109:Acetylcholine