N omega-nitro-L-arginine constricts cerebral arterioles without increasing intracellular calcium levels.
The coupling between intracellular Ca2+ concentration ([Ca2+]i) and smooth muscle cell (SMC) contractility is well known, but recent reports suggest that SMCs can contract without an increase in [Ca2+]i. Penetrating arterioles were isolated from rat cortex, cannulated, and loaded extraluminally with fura 2. We used ratio imaging of corresponding vessel wall areas to estimate and correlate [Ca2+]i to the vessel diameter during various extraluminal treatments. Control diameter was 45.6 +/- 3.9 (SE) microns with an estimated [Ca2+]i of 181 +/- 18 nM. Extraluminal papaverine or pH of 6.8 dilated the vessels to 61.0 +/- 6.6 and 57.8 +/- 5.8 microns and decreased [Ca2+]i to 108 +/- 33 and 155 +/- 8 nM, respectively. Alkaline pH of 7.65 or the Ca2+ ionophore ionomycin constricted the arterioles to 34.8 +/- 3.9 and 30.0 +/- 5.8 microns and increased [Ca2+]i to 273 +/- 47 and 853 +/- 155 nM, respectively. These results show an inverse relationship between vessel diameter and [Ca2+]i. Blocking the production of endothelium-derived nitric oxide (EDNO) with N omega-nitro-L-arginine constricted the vessels to 34.4 +/- 3.5 microns without raising but lowering [Ca2+]i to 157 +/- 44 nM. The dissociation of vessel tone and estimated [Ca2+]i after EDNO blocking has not been reported before in cerebral arterioles and may indicate that EDNO regulates vascular tone in a Ca(2+)-independent manner.
Dietrich
H H
HH
Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri 63110.
Kimura
M
M
Dacey
R G
RG
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016257:Fura-2; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D002118:Calcium; D016257:Fura-2