Effects of nitric oxide synthase inhibition and low-salt diet on blood pressure and mesenteric resistance artery remodelling in genetically hypertensive rats.
1. Nitric oxide synthase (NOS)-inhibited genetically hypertensive (GH) rats on normal and low-sodium diets were additionally given valsartan or felodipine to establish whether low-Na intake would have extra beneficial effects on blood pressure and cardiovascular structure. 2. Male GH rats on normal or low-Na diets were treated with the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) from the age of 7 to 12 weeks and were given either valsartan (10 mg/kg per day) or felodipine (30 mg/kg per day). 3. Systolic blood pressure (SBP; tail-cuff) was measured weekly. At 12 weeks of age, mesenteric resistance arteries (MRA) were fixed by perfusion and embedded in Technovit (Heraeus Kulzer GmbH, Werheim, Germany). Serial sections were cut and stained. Stereological analysis was used to obtain MRA media width, lumen diameter, ratio of media width/lumen diameter (M/L) and medial cross-sectional area (CSA). Left ventricular (LV) mass was determined. 4. In GH L-NAME-treated rats on a normal diet, SBP was significantly reduced (P < 0.001) by valsartan and felodipine, as was LV mass (valsartan P < 0.001; felodipine P < 0.05). A low-Na diet with valsartan caused a further fall in SBP (P < 0.01) but, with felodipine, SBP increased in rats on a low-Na diet (P < 0.05). 5. Valsartan with the low-Na diet had no further effect on LV mass, but the felodipine-treated group on a low-Na diet had a lower LV mass (P < 0.05) than rats on a normal diet. 6. In MRA from the GH L-NAME + valsartan-treated group, there was hypotrophic inward remodelling; the M/L ratio was reduced (P < 0.001) compared with GH L-NAME-treated rats. The lumen was outwardly remodelled in the group on the low-Na diet. 7. The GH L-NAME + felodipine-treated group showed hypotrophic outward remodelling and a reduction in M/L ratio compared with the GH L-NAME-treated group (P < 0.001). A low-Na diet had no further effect on MRA. 8. A low-Na diet + valsartan had beneficial effects on SBP and MRA, where outward remodelling of the lumen occurred and, thus, resistance was reduced. In contrast, felodipine with a low-Na diet increased SBP, reduced LV mass and had no effect on MRA structure. Valsartan treatment with a low-Na diet confers extra benefits on blood pressure and MRA structure.
Ledingham
J M
JM
Department of Pharmacology, School of Medical Sciences, University of Otago, Dunedin, New Zealand. janet.ledingham@stonebow.otago.ac.nz
Laverty
R
R
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D011918:Rats, Inbred SHR; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D013599:Systole; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan; D014655:Vascular Resistance
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; D000068756:Valsartan; D019001:Nitric Oxide Synthase; D014633:Valine; D019331:NG-Nitroarginine Methyl Ester