Altered nitric oxide synthase 3 distribution in mesenteric arteries of hypertensive rats.
A high-salt (HS) diet and angiotensin II (Ang II) are both associated with the development of hypertension and impaired endothelial function. We hypothesize that alterations in nitric oxide synthase (NOS) activity or subcellular localization of NOS 3 protein may contribute to endothelial dysfunction in salt-dependent hypertension. To test this hypothesis, two models of salt-dependent hypertension were studied: DOCA-salt and Ang II. For Ang II hypertension, rats were divided into 4 groups: control on normal or HS diet, Ang II-infused on normal or HS diet. The mesenteric arterial bed was isolated and frozen in liquid nitrogen. Frozen arteries were homogenized and separated into cytosolic and particulate fractions. NOS activity was assayed by determining the conversion of (3)H-arginine to (3)H-citrulline in the absence and presence of the NOS inhibitor, Nomega-nitro-L-arginine. NOS 3 protein expression was significantly increased in the cytosol of arteries from DOCA-salt compared with placebo rats and in Ang II-infused and Ang HS rats compared with control. NOS 3 expression in the particulate fraction was comparable among all groups. NOS activity (pmol/30 min/total protein) was significantly increased in the cytosolic fraction of arteries from DOCA-salt rats compared with placebo and in Ang HS rats compared with control. NOS activity was comparable in the particulate fraction in all rat groups. In conclusion, there is an altered subcellular distribution of NOS 3 in salt-dependent hypertension that may contribute to the development of hypertension and endothelial dysfunction.
Sullivan
Jennifer C
JC
Vascular Biology Center, Department of Pharmacology, Medical College of Georgia, Augusta, GA 30912, USA.
Pollock
David M
DM
Pollock
Jennifer S
JS
D000818:Animals; D001794:Blood Pressure; D004032:Diet; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017207:Rats, Sprague-Dawley; D012492:Salts; D013347:Subcellular Fractions
D007527:Isoenzymes; D012492:Salts; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat