Increased vasoconstrictor reactivity and decreased endothelial function in high grade varicocele; functional and morphological study

The pathophysiology of human varicocele is not fully understood. We investigated vasoconstrictor reactivity, endothelial function and morphological changes in different grades of varicocele to clarify the pathophysiology. Contractile responses to phenylephrine, norepinephrine, serotonin and histamine were determined in isolated human varicose spermatic veins using the organ bath technique. Endothelial function was tested with acetylcholine-induced relaxation after phenylephrine-induced precontraction in the absence and presence of nitric oxide synthase inhibitor, L-NAME, and cyclooxygenase inhibitor, indomethacin. The cyclic guanosine monophosphate (cGMP) level was measured in the spermatic vein and peripheral plasma. Morphological changes were evaluated with light microscopy. Phenylephrine, norepinephrine, serotonin and histamine induced concentration-dependent contractions. The maximum contractions for all of these agents except norepinephrine were significantly higher in grade III than grade I and II (P<0.05). The sensitivity to phenylephrine was significantly higher in grades II and III than in grade I (P<0.05). In the presence of L-NAME and indomethacin, the difference from respective control phenylephrine-induced contractions was higher in grade I and II than grade III. Acetylcholine did not induce stable relaxation but the level of cGMP, which is responsible for the vasorelaxant effect of NO, in veins was lower in grades II and III than grade I (P<0.05). Vessel wall thickness increased in grade II and dilatation developed in grade III when compared to grade I (P<0.05). Our findings suggest that endothelium produces less vasorelaxant which results in the more enhanced effects of vasoconstrictor substances in grade III, indicating that endothelial dysfunction develops at high grades of varicocele.