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ATP‐induced local and conducted vasomotor mechanisms in isolated rat cerebral penetrating arterioles
Author(s) -
Dietrich Hans H.,
Horiuchi Tetsuyoshi,
Falck J. Russel,
Dacey Ralph G.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a730-b
Subject(s) - hyperpolarization (physics) , vasomotor , nitric oxide , vasodilation , cerebral circulation , chemistry , medicine , vascular smooth muscle , endothelium , endocrinology , anatomy , anesthesia , biophysics , biology , organic chemistry , smooth muscle , nuclear magnetic resonance spectroscopy
Background ATP is a regulator in the cerebral circulation and initiates conducted vasomotor responses. We analyzed the mechanism of ATP‐induced local and conducted vasomotor responses in rat cerebral penetrating arterioles. Methods Arterioles were cannulated and their internal diameter monitored with a video microscope. Vasomotor responses to micro‐application of ATP were obtained in the presence or absence of inhibitors. Intracellular membrane potentials of smooth muscle cells were measured in some vessels. Results Topical micro‐application of ATP produced a biphasic response (constriction followed by dilation), resulting in conducted vasomotor responses. Conducted dilation was preceded by membrane hyperpolarization. a.b‐methylene‐ATP or pyridoxal phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid blunted the ATP‐mediated constriction and enhanced the dilation. No‐monomethyl‐L‐arginine, clotrimazole, and endothelial impairment inhibited the local dilation of ATP. In contrast, the conducted dilation was attenuated by clotrimazole, MS‐PPOH and endothelial impairment, but not No‐monomethyl‐L‐arginine. Conclusions Our results indicate that 1) ATP‐induced conducted dilation is preceded by hyperpolarization; 2) ATP induces initial local constriction via smooth muscle P2X1 and secondary dilation via endothelial P2Y2 receptors in the cerebral arterioles; 3) Nitric oxide and cytochrome P‐450 metabolites contribute to local dilation of ATP; 4) ATP‐induced conducted dilation is regulated by the endothelium and cytochrome P‐450 metabolites. NIH HL57540 (HHD) and NS30555 (RGD and HHD).