In vivo and in vitro effects of nebivolol on penile structures in hypertensive rats.
BACKGROUND
Erectile dysfunction is associated with high blood pressure and antihypertensive treatment, especially diuretics and traditional beta-blockers. Nevertheless, new beta-blockers such as nebivolol present some differences with respect to the classic beta-blockers. The aim of this study was to determine the functional and morphologic effects of nebivolol on penile structures in hypertensive rats.


METHODS
During a 6-month period, male spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rats were studied. The groups were as follows: 1) untreated SHR (Untreated-SHR); 2) SHR given nebivolol 10 mg/kg/day (SHR+N); 3) SHR given amlodipine 3 mg/kg/day (SHR+AML); and 4) untreated WKY (untreated-WKY). Cavernous smooth muscle (CSM) and vascular smooth muscle (VSM) from cavernous arteries, as well as collagen type III (COL III) in cavernous tissue, were evaluated.


RESULTS
After 6 months, SHR groups given nebivolol and amlodipine showed similar reductions in blood pressure compared with untreated SHR. However, only SHR+N and control WKY showed significantly lower values of CSM (P < 01), VSM (P < 01), and COL III (P < 01) when compared with untreated SHR and SHR+AML. In addition SHR+N showed a higher endothelial nitric oxide synthase expression in sinusoidal endothelium compared with SHR, and SHR+AML (P < 01). In vitro studies revealed that SHR+N displayed a better relaxation response to acetylcholine than untreated-SHR and SHR+AML (P < 01).


CONCLUSIONS
Nebivolol presented equivalent BP control compared with amlodipine. However, only nebivolol showed a significant better functional outcome with a protective role against structural changes in erectile tissue that are caused by arterial hypertension.
Toblli
Jorge Eduardo
JE
Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina. jtobilli@hospitalaleman.com
Cao
Gabriel
G
Casas
Gabriel
G
Mazza
Osvaldo Néstor
ON
D000109:Acetylcholine / Q000494:pharmacology; D000199:Actins / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D000068577:Nebivolol; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010413:Penis / Q000098:blood supply / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D000109:Acetylcholine; D000199:Actins; D000319:Adrenergic beta-Antagonists; D017311:Amlodipine; D000959:Antihypertensive Agents; D001578:Benzopyrans; D003094:Collagen; D004983:Ethanolamines; D000068577:Nebivolol; D052250:Nitric Oxide Synthase Type III; D010656:Phenylephrine; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C498862:Acta2 protein, rat; C496316:Nos3 protein, rat