Functional role of the Na+/H+ exchanger in the regulation of cerebral arteriolar tone in rats.
OBJECTIVE
In vascular smooth-muscle cells, the Na+/H+ exchanger (NHE) is involved in the regulation of [Na+]i, pHi through [H+], and cell volume. Recently, investigations have determined that this exchanger contributes to ischemia and reperfusion injury in coronary circulation. Nonetheless, there is limited information on this glycoprotein in cerebral circulation, especially microcirculation. Thus, the authors in the present study examined the role of NHE in the regulation of cerebral arteriolar tone and its related mechanisms in vitro.


METHODS
The internal diameter of isolated pressurized intracerebral arterioles in rats was monitored with the aid of a microscope. To examine the basal activity of NHE two kinds of Na+/H+ exchange inhibitors (FR183998 and 5-[N,N-hexamethylene]amiloride) were administered in the arterioles. Furthermore the authors studied the effects of nitric oxide (NO) synthase inhibitor (NG methyl-L-arginine), Na+/K+ -adenosine triphosphatase (NKA) inhibitor (ouabain), and the Na+/Ca++ exchange inhibitor (SEA0400) on the vascular response induced by either of the Na+/H+ exchange inhibitors. Both of the Na+/H+ exchange inhibitors constricted the arteriole. Subsequent application of NO synthase inhibitor further decreased the diameter of the arterioles. The Na+/H+ exchange inhibitor-induced constriction was completely abolished in the presence of ouabain and SEA0400.


CONCLUSIONS
The NHE is active in the basal condition and regulates cerebral arteriolar tone through NKA and the Na+/Ca++ exchanger. Endogenous NO is not related to the activity of NHE in basal conditions.
Department of Neurosurgery, Shinshu University School of Medicine, Matsumoto, Japan.
Prajak
P
Saesue
Tetsuyoshi
T
Horiuchi
Tetsuya
T
Goto
Yuichiro
Y
Tanaka
Kazuhiro
K
Hongo
D000584:Amiloride / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000814:Aniline Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply* / Q000201:enzymology / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008833:Microcirculation / Q000378:metabolism; D015288:Neurokinin A / Q000031:analogs & derivatives*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010446:Peptide Fragments; D010647:Phenyl Ethers / Q000008:administration & dosage / Q000494:pharmacology; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors; D017923:Sodium-Hydrogen Exchangers; D000254:Sodium-Potassium-Exchanging ATPase / Q000008:administration & dosage / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D000097795:ATPase Inhibitory Protein
D000584:Amiloride; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D015288:Neurokinin A; D019001:Nitric Oxide Synthase; D010446:Peptide Fragments; D010647:Phenyl Ethers; D010750:Phosphoproteins; D011506:Proteins; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D000254:Sodium-Potassium-Exchanging ATPase; D000097795:ATPase Inhibitory Protein; C430918:SEA 0400; C079306:neurokinin A (4-10)-OH; C093376:sodium-hydrogen exchanger regulatory factor; C057360:5-(N,N-hexamethylene)amiloride