Possible role of bradykinin and angiotensin II in the regulation of penileerection and detumescence

Objectives. To examine the functional effects of bradykinin (BK) and angiot ensin II (AN II) on isolated human cavernous tissue and to detect any chang es in the AN II levels in cavernous and peripheral blood samples taken from healthy volunteers at different functional conditions of the penile erecti le tissue. Metabolites of the renin-angiotensin system and endothelium-deri ved vasoactive substances are known to be involved in the regulation of art erial vascular tone. The human corpus cavernosum (HCC), consisting of endot helial and smooth muscle cells, can be regarded as a compartment comparable to the vascular system. Methods. The relaxing and contracting properties of BK and AN II on isolate d HCC were investigated using the organ bath technique. Tissue levels of ad enosine-3,5-cyclic monophosphate (cAMP) and guanosine-3,5-cyclic monophosph ate (cGMP) were determined using specific radioimmunoassays, after exposing isolated HCC strips in a dose-dependent manner to BK, forskolin, and sodiu m nitroprusside. Blood samples were drawn simultaneously from the corpus ca vernosum and cubital vein of 34 healthy volunteers at stages of penile flac cidity, tumescence, rigidity, and detumescence. Penile erection was induced by audiovisual and tactile stimulation. AN II levels were determined using a radioimmunoassay. Results. In vitro, BK, forskolin, and sodium nitroprusside elicited dose-de pendent relaxation of norepinephrine-induced tension of isolated HCC, and A N II evoked dose-dependent contraction of the HCC strips. The relaxing pote ncy of BK was paralleled by its ability to elevate the intracellular levels of cAMP and cGMP. In vivo, the AN II levels in the cavernous plasma increa sed from 21.8 +/- 4.6 pg/mL in the flaccidity phase to 27.9 +/- 10 pg/ml in the detumescence phase. in the peripheral plasma, the AN II levels were 17 .2 +/- 6.2 to 19.5 +/- 6.5 pg/mL in the respective penile stages. Thus, the mean AN II levels in the cavernous blood were about 30% higher than in the blood samples taken from the cubital vein. In the cavernous blood, the inc rease in the AN II plasma levels in the detumescence phase (27.9 +/- 10 pg/ mL) was statistically significant. Conclusions. Our results suggest that penile cavernous smooth muscle tone i s partially balanced by kinin-induced relaxation and AN It-induced contract ion. Since the tissue and plasma levels of both peptides are regulated by t he activity of the angiotensin-converting enzyme, th ere might be a rationa le for the use of angiotensin-converting enzyme inhibitors in the treatment of erectile dysfunction associated with arterial hypertension. UROLOGY 57: 193-198, 2001. (C) 2001, Elsevier Science Inc.