Erectile function in two-kidney, one-clip hypertensive rats is maintained by a potential increase in nitric oxide production.
BACKGROUND
Hypertension is closely associated with erectile dysfunction (ED) as it has been observed in many experimental models of hypertension. Additionally, epidemiological studies show that approximately a third of hypertensive patients have ED.


OBJECTIVE
To test the hypothesis that the two-kidney, one-clip (2K-1C) rat model of hypertension displays normal erectile function due to increased nitric oxide (NO) production in the penis.


METHODS
Ganglionic-induced increase in intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio was used as an index of erectile function in 2K-1C and in normotensive sham-operated (SHAM) anesthetized rats. Cavernosal strips from hypertensive and normotensive rats were used for isometric tension measurement. The contraction induced by alpha-adrenergic agonist phenylephrine and the relaxation induced by the NO donor sodium nitroprusside (SNP) and by the Rho-kinase inhibitor Y-27632 were performed in the absence and in the presence of the NO synthase inhibitor N(omega)-nitro-L-arginine (L-NNA).


RESULTS
Changes in ICP/MAP induced by ganglionic stimulation were not different between 2K-1C and SHAM rats. The contractile response induced by phenylephrine as well as the relaxation induced by SNP or the Y-27632 were similar in cavernosal strips from both groups. However, in the presence of L-NNA, the relaxation induced by Y-27632 was significantly impaired in 2K-1C compared to SHAM.


CONCLUSIONS
These data suggest that hypertension and ED could be dissociated from high levels of blood pressure in some animal models of hypertension. Erectile function in 2K-1C hypertensive rats is maintained in spite of the increased Rho-kinase activity by increased NO signaling.
Linder
A Elizabeth
AE
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
Dorrance
Anne M
AM
Mills
Thomas M
TM
Webb
R Clinton
RC
Leite
Romulo
R
D000577:Amides / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D007172:Erectile Dysfunction / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D045888:Ganglion Cysts / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology / Q000627:therapeutic use; D010413:Penis / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology / Q000627:therapeutic use; D011312:Pressure; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
D000577:Amides; D000959:Antihypertensive Agents; D011725:Pyridines; C108830:Y 27632; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D054460:rho-Associated Kinases; D007213:Indomethacin