EFFECT OF N-G-NITRO-L-ARGININE METHYL-ESTER ON TESTICULAR BLOOD-FLOW AND SERUM STEROID-HORMONES DURING SEPSIS

Production of nitric oxide (NO) via NO synthase (NOS) has been implica ted in the regulation of steroidogenesis in normal physiology and sept ic pathophysiology. The hypothesis that blockade of NOS by N-G-nitro-L -arginine methyl ester (L-NAME) would affect testicular blood flow and circulating levels of steroid reproductive hormones was tested. Male Sprague-Dawley rats (350-450 g) were randomized to septic and nonsepti c groups. Sepsis was induced with an intraperitoneal (i.p.) injection of a cecal slurry (200 mg/kg in 5 mL 5% dextrose in water (D5W)) in ra ts, while nonseptic rats received only sterile D5W. The rats (n = 6 pe r group) were catheterized in the jugular vein, left ventricle (via ri ght carotid artery), and tail artery to determine blood flow and syste mic hemodynamics and to collect blood at 24 h after induction of sepsi s/sham sepsis. After baseline (24 h post-cecal slurry challenge) measu rement, L-NAME (.50 mg/kg.min) was infused through the jugular vein fo r 10 min, blood flow was determined using a radioactive microsphere te chnique, and blood samples were collected. The serum concentrations of corticosterone, progesterone, and testosterone were determined using radioimmunoassay. Plasma concentrations of NO byproducts (NOx) were de termined using the Greiss reaction. After 24 h, heart rate, testicular blood flow, and NOx levels were significantly increased, whereas the serum concentration of testosterone was significantly decreased in the septic group as compared with the nonseptic group. However, serum con centrations of progesterone and corticosterone at 24 h after induction of sham-sepsis or sepsis were not statistically different. Infusion o f L-NAME significantly reduced the testicular blood flow and serum NOx levels in septic rats as compared with their baseline values. The adm inistration of L-NAME significantly increased the concentration of tes tosterone in nonseptic and septic rats as compared with their respecti ve basal values. However, testosterone levels in septic rats were stil l significantly lower than in nonseptic rats. The results of this stud y indicate that the synthesis of NO through NO synthase may play a rol e in the regulation of testicular blood flow and the serum levels of t estosterone, associated with chronic peritoneal sepsis in the rat.