Inhibition of nitric oxide synthase by NG-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 NG-nitro-L-arginine (N-arg; 25 mg/kg BW) was administered iv to rats 10 min before pancreatic blood flow was measured with a nonradioactive microsphere technique. In male Sprague-Dawley rats, N-arg induced a marked decrease in islet blood flow (16 +/- 4 vs. 44 +/- 8 microliters/min.g pancreas; P < 0.001) and a less pronounced decrease in whole pancreatic blood flow (0.27 +/- 0.04 vs. 0.43 +/- 0.06 ml/min.g; P < 0.05), leading to a markedly decreased 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 blood flow (P < 0.05). Such an increase has previously been shown to be mediated by a vagal cholinergic mechanism. Administration of N-arg to these rats resulted in decreased pancreatic (P < 0.05), islet (P < 0.001), 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 F1-hybrids of the GK (Goto-Kakizaki) rat, a spontaneous animal model of noninsulin-dependent diabetes mellitus. Administration of N-arg to female 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 observed in female Wistar rats treated in parallel. These data are consistent with the possibility that NO is an important physiological regulator of islet blood flow. Furthermore, the vagally dependent high levels of islet blood flow demonstrated in the GK rat appear to be mediated by a mechanism involving NO.
Svensson
A M
AM
Department of Medical Cell Biology, Uppsala University, Sweden.
Ostenson
C G
CG
Sandler
S
S
Efendic
S
S
Jansson
L
L
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D007515:Islets of Langerhans / Q000098:blood supply*; D008297:Male; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects
D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases