INHIBITION OF NITRIC-OXIDE SYNTHASE BY N-G-NITRO-L-ARGININE CAUSES A PREFERENTIAL DECREASE IN PANCREATIC-ISLET BLOOD-FLOW IN NORMAL RATS AND SPONTANEOUSLY DIABETIC GK RATS

To elucidate the effect of nitric oxide (NO) on the blood flow of the pancreatic islets, the NO synthase inhibitor N-G-nitro-L-arginine (N-a rg; 25 mg/kg BW) was administered iv to rats 10 min before pancreatic blood flow was measured with a nonradioactive microsphere technique. I n male Sprague-Dawley rats, N-arg induced a marked decrease in islet b lood flow (16 +/- 4 vs. 44 +/- 8 mu l/min.g pancreas; P < 0.001) and a less pronounced decrease in whole pancreatic blood flow (0.27 +/- 0.0 4 vs. 0.43 +/- 0.06 ml/min.g; P < 0.05), leading to a markedly decreas ed fractional islet blood flow (5.5 +/- 0.9% vs. 10.3 +/- 1.3%; P < 0. 02). In a second experiment, injection of D-glucose (300 mg/kg BW, iv) in male Sprague-Dawley rats induced a selective increase in islet blo od flow (P < 0.05). Such an increase has previously been shown to be m ediated by a vagal cholinergic mechanism. Administration of N-arg to t hese rats resulted in decreased pancreatic (P < 0.05), islet (P < 0.00 1), and fractional (P < 0.001) islet blood flow, which did not differ from those observed in normoglycemic rats after treatment with N-arg. Furthermore, we studied the mechanism behind the previously described increase in islet blood perfusion, mediated by the vagus nerve, in F-1 -hybrids of the GK (Goto-Kakizaki) rat, a spontaneous animal model of noninsulin-dependent diabetes mellitus. Administration of N-arg to fem ale GK rats resulted in decreases in islet (P < 0.001), pancreatic (P < 0.01), and fractional islet blood flow (P < 0.001) to the levels obs erved in female Wistar rats treated in parallel, These data are consis tent with the possibility that NO is an important physiological regula tor of islet blood flow. Furthermore, the vagally dependent high level s of islet blood flow demonstrated in the GK rat appear to be mediated by a mechanism involving NO.