Regional heterogeneity in the mechanisms of myogenic tone in hamster arterioles.

Myogenic tone is an important feature of arterioles and resistance arteries, but the mechanisms responsible for this hallmark characteristic remain unclear. We used pharmacological inhibitors to compare the roles played by phospholipase C (PLC; 10 μM U73122), inositol 1,4,5-trisphosphate receptors (IPRs; 100 μM 2-aminoethoxydiphenylborane), protein kinase C (10 μM bisindolylmaleimide I), angiotensin II type 1 receptors (1 μM losartan), Rho kinase (10 nM-30 μM Y27632 or 300 nM H1152), stretch-activated ion channels (10 nM-1 μM Gd or 5 μM spider venom toxin GsMTx-4) and L-type voltage-gated Ca channels (0.3-100 μM diltiazem) in myogenic tone of cannulated, pressurized (80 cmHO), second-order hamster cremaster or cheek pouch arterioles. Effective inhibition of either PLC or IPRs dilated cremaster arterioles, inhibited Ca waves, and reduced global Ca levels. In contrast, cheek pouch arterioles did not display Ca waves and inhibition of PLC or IPRs had no effect on myogenic tone or intracellular Ca levels. Inhibition of Rho kinase dilated both cheek pouch and cremaster arterioles with equal efficacy and potency but also reduced intracellular Ca signals in both arterioles. Similarly, inhibition of mechanosensitive ion channels with Gd or GsMTx-4 produced comparable dilation in both arterioles. Inhibition of L-type Ca channels with diltiazem was more effective in dilating cremaster (86 ± 5% dilation, = 4) than cheek pouch arterioles (54 ± 4% dilation, = 6, < 0.05). Thus, there are substantial differences in the mechanisms underlying myogenic tone in hamster cremaster and cheek pouch arterioles. Regional heterogeneity in myogenic mechanisms could provide new targets for drug development to improve regional blood flow in a tissue-specific manner. Regional heterogeneity in the mechanisms of pressure-induced myogenic tone implies that resistance vessels may be able to alter myogenic signaling pathways to adapt to their environment. A better understanding of the spectrum of myogenic mechanisms could provide new targets to treat diseases that affect resistance artery and arteriolar function.