TISSUE ANGIOTENSIN-II AS A MODULATOR OF ERECTILE FUNCTION .1. ANGIOTENSIN PEPTIDE CONTENT, SECRETION AND EFFECTS IN THE CORPUS CAVERNOSUM

Purpose: Although Angiotensin II (Ang II) is a major modulator of regi onal blood flow in the extracavernosal segments of the vascular bed, i ts role in erectile function is unknown. The corpus cavernosum penis i s a modified vascular tissue that contains endothelial and smooth musc le cells. In other segments of the vascular bed, these cell types prod uce Ang II. Therefore, we explored the presence and function of an Ang II producing paracrine system in the corpus cavernosum. Methods: The angiotensin content of the human corpus cavernosum was measured by rad ioimmunoassay. The distribution pattern of Ang II containing cells wit hin the corpus cavernosum was assessed by an immunohistochemical techn ique, and the rate of its secretion was determined by superfusion. The effects of Ang II and its antagonist, losartan, on intracavernosal pr essure were determined under in vivo conditions, in anesthetized dogs. Results: Human corpus cavernosum contained 1178 +/- 223 (SEM) fmol An g II, 528 +/- 171 fmol Ang I, 475 +/- 67 fmol des-asp-Ang I, and 1897 +/- 371 fmol des-asp-Ang II/gm. tissue (n = 4). Ang II was found mainl y in endothelial cells lining blood vessels and smooth muscle bundles within the corpus cavernosum. Superfused cavernosal tissue secreted im mune-reactive Ang II (Ang II,) at a rate of 57 +/- 36.5 fmol Ang IIir/ gm. tissue/minute (n = 10). The amount of Ang II released per gram of tissue in an hour was 3-fold greater than the Ang II content/gm. tissu e, suggesting a local production of Ang II. Papaverine and prostagland in E-1 suppressed Ang II secretion significantly (p < 0.001, p = 0.013 ). The responsiveness to inhibition was a function of the initial rate of Ang II secretion. Tissue samples with a high rate of secretion wer e less responsive to the inhibitors than tissue that secreted small am ounts of Ang II (n = 6). In anesthetized dogs, intra-cavernosal inject ion of Ang II terminated spontaneous erections, while losartan increas ed the intracavernosal pressure in a dose dependent manner up to the m ean arterial pressure (n = 4). Conclusions: The corpus cavernosum prod uces and secretes physiologically relevant amounts of Ang II. The rate of Ang II secretion can be modulated by pharmacologic agents that reg ulate cytosolic calcium levels and are used clinically to treat erecti le dysfunction. Intracavernosal injection of Ang II causes contraction of cavernosal smooth muscle and terminates spontaneous erection in an esthetized dog, while administration of an Ang II receptor antagonist results in smooth muscle relaxation and thus erection.