beta-Adrenoceptor and nNOS-derived NO interactions modulate hypoglycemic pial arteriolar dilation in rats

We examined the relative contributions from nitric oxide (NO) and catechola minergic pathways in promoting cerebral arteriolar dilation during hypoglyc emia (plasma glucose congruent to 1.4 mM). To that end, we monitored the ef fects of beta -adrenoceptor (beta -AR) blockade with propranolol (Pro, 1.5 mg/kg iv), neuronal nitric oxide synthase (nNOS) inhibition with 7-nitroind azole (7-NI, 40 mg/kg ip) or ARR-17477 (300 muM, via topical application), or combined intravenous Pro + 7-NI or ARR-17477 on pial arteriolar diameter changes in anesthetized rats subjected to insulin-induced hypoglycemia. Ad ditional experiments, employing topically applied TTX (1 muM), addressed th e possibility that the pial arteriolar response to hypoglycemia required ne uronal transmission. Separately, Pro and 7-NI elicited modest but statistic ally insignificant 10-20% reductions in the normal similar to 40% increase in arteriolar diameter accompanying hypoglycemia. However, combined Pro-7-N I was accompanied by a >80% reduction in the hypoglycemia-induced dilation. On the other hand, the combination of intravenous Pro and topical ARR-1747 7 did not affect the hypoglycemia response. In the presence of TTX, the pia l arteriolar response to hypoglycemia was lost completely. These results su ggest that 1) beta -ARs and nNOS-derived NO interact in contributing to hyp oglycemia-induced pial arteriolar dilation; 2) the interaction does not occ ur in the vicinity of the arteriole; and 3) the vasodilating signal is tran smitted via a neuronal pathway.