In hamster cremaster muscle, capillary networks consist of anatomically invariant subunits termed modules [Berg, B. R., and I. H. Sarelius, Am. J. Physiol. 268 (Heart Circ. Physiol. 37): H1215-H1222, 1995]. To explore local coupling between blood flow and metabolism, we used micropipettes to stimulate five to six muscle fibers running underneath specified capillary modules. Capillary erythrocyte flow increased significantly at all stimulation frequencies because of increased erythrocyte content at 2 Hz and increased erythrocyte velocity at 4 and 8 Hz. Erythrocyte flow did not increase when the fibers underlying the module were mechanically tugged but did not actively contract at these frequencies. Increased capillary flow was accommodated by dilation of three upstream arteriolar generations: the module inflow arteriole dilated significantly at all frequencies, and further upstream, dilations were significant at higher frequencies. Other module inflow arterioles in the same capillary network as the stimulated module did not dilate. Dilations in the module inflow arteriole were abolished by 600 mosM sucrose but were unaffected by 10(-6) M tetrodotoxin. These data suggest that local coupling between capillary flow and muscle contraction includes a conducted vasodilation that is responsible for the remote upstream dilations.

Elevated [K+]o causes transient vasodilation of skeletal muscle arterioles that appears to be an intrinsic property of the arterioles. The results suggest that K+-induced dilation involves activation of both the Na+/K+ ATPase and KIR channels, leading to membrane hyperpolarization, a fall in [Ca2+]i, and culminating in vasodilation. The Na+/K+ ATPase appears to play the major role and is largely responsible for the transient nature of the response to elevated [K+]o, whereas KIR channels primarily affect the duration and kinetics of the response.

In hamster cremaster muscle, it has been shown previously that contraction of skeletal muscle fibers underlying small groups of capillaries (modules) induces dilations that are proportional to metabolic rate in the two arteriolar generations upstream of the stimulated capillaries (Berg BR, Cohen KD, and Sarelius IH. Am J Physiol Heart Circ Physiol 272: H2693-H2700, 1997). These remote dilations were hypothesized to be transmitted via gap junctions and not perivascular nerves. In the present study, halothane (0.07%) blocked dilation in the module inflow arteriole, and dilation in the second arteriolar generation upstream, the branch arteriole, was blocked by both 600 mosM sucrose and halothane but not tetrodotoxin (2 microM). Dilations in both arterioles were not blocked by the gap junction uncoupler 18-beta-glycyrrhetinic acid (40 microM), and 80 mM KCl did not block dilation of the module inflow arteriole. These data implicate a gap junctional-mediated pathway insensitive to 18-beta-glycyrrhetinic acid in dilating the two arterioles upstream of the capillary module during "remote" muscle contraction. Dilation in the branch arteriole, but not the module inflow arteriole, was attenuated by 100 microM N(omega)-nitro-L-arginine. Thus selective contraction of muscle fibers underneath capillaries results in dilations in the upstream arterioles that have characteristics consistent with a signal that is transmitted along the vessel wall through gap junctions, i.e., a conducted vasodilation. The observed insensitivities to 18-beta-glycyrrhetinic acid, to KCl, and to N(omega)-nitro-L-arginine suggest, however, that there are multiple signaling pathways by which remote dilations can be initiated in these microvessels.

Background and purpose: a 1 -Adrenoceptor agonists induce Ca 2 þ -transients in endothelial cells (ECs) of arterioles. However, the presence of a 1 -adrenoceptors on arteriolar ECs has not been excluded, and the identity of a 1 -adrenoceptor subtypes in arterioles only has been inferred from pharmacology. Therefore, we determined which subtypes were expressed by vascular smooth muscle cells (VSMCs) and ECs, and which subtype mediated a 1 -adrenoceptor-induced constriction. Experimental approach: EC Ca 2 þ -transients in isolated, cannulated hamster cremasteric arterioles or freshly isolated ECs were studied using Fura 2. Arteriolar diameter was measured by video microscopy. a 1 -Adrenoceptor expression was assessed by western blot of whole-arteriolar homogenates and real-time RT-PCR on enzymatically isolated VSMCs and ECs. Key results: Phenylephrine-induced constriction and EC Ca 2 þ -transients were abolished by the a 1 -adrenoceptor antagonist prazosin (30 nM) in arterioles. Phenylephrine-induced constriction was inhibited by the a 1D -adrenoceptor antagonist BMY 7378 (K B ¼ 2.96 nM) and the a 1A -adrenoceptor antagonist 5-methylurapidil (K B ¼ 4.08 nM), suggesting a significant role for a 1D -adrenoceptors. Western blots confirmed a 1D -adrenoceptor expression, but did not detect a 1A -adrenoceptors. VSMCs expressed a 1D -and a 1A -, but not a 1B -, adrenoceptor transcripts. No a 1 -adrenoceptor transcripts were detected in ECs. Neither phenylephrine (10 mM) nor noradrenaline (0.1-1 mM) elicited Ca 2 þ -transients in freshly isolated ECs, whereas the endotheliumdependent vasodilators methacholine (1 mM) and substance P (100 nM) consistently increased Ca 2 þ . Conclusions and implications:We reject the hypothesis that hamster cremasteric arteriolar ECs express a 1 -adrenoceptors and conclude that a 1 -adrenoceptor agonists predominantly act on VSMC a 1D -adrenoceptors to cause vasoconstriction and a subsequent rise in EC Ca 2 þ .