Effect of Angiotensin II and its Receptor Antagonists on Human Corpus Cavernous Contractility and Oxidative Stress: Modulation of Nitric Oxide Mediated Relaxation

Abstract

To our knowledge the interaction between angiotensin II and nitric oxide in the control of human corpus cavernous function has not been assessed previously. We determined the presence and role of angiotensin II and its receptors in human penile function. Corpus cavernous tissue was obtained from 35 patients undergoing gender reassignment surgery. Immunohistochemical analysis was done to determine angiotensin II peptide tissue distribution. Organ bath studies were done to determine the angiotensin II/nitric oxide interaction on corpus cavernous smooth muscle function. The role of oxidative stress in the angiotensin II response was also examined using the nicotinamide adenine dinucleotide phosphate oxidase inhibitor apocynin. Angiotensin II was distributed in arteriolar endothelium, endothelium lining sinusoids and smooth muscle cells, and caused dose dependent contraction of human corpus cavernous smooth muscle strips that was inhibited by the angiotensin type 1 receptor antagonist losartan. Relaxation of corpus cavernous smooth muscle induced by the nitric oxide donor sodium nitroprusside or electrical field stimulation was potentiated by losartan. Apocynin decreased angiotensin II induced corpus cavernous contraction. Angiotensin II and nitric oxide interact to modulate human cavernous function since losartan potentiated sodium nitroprusside and electrical field stimulation mediated corpus cavernous smooth muscle relaxation. The angiotensin II response involves the production of superoxide and the development of oxidative stress. These findings support the role of angiotensin II in the regulation of human penile smooth muscle tone and suggest that angiotensin type 1 receptor inhibition may be a therapeutic approach to erectile dysfunction.