Nitric oxide synthase inhibition with N omega-nitro-L-arginine methyl ester affects blood pressure and cardiovascular structure in the genetically hypertensive rat strain.
1. Inhibition of nitric oxide (NO) synthesis with the nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) was used as a tool to investigate further a possible endothelial defect in the New Zealand genetically hypertensive (GH) rat strain compared with its normotensive (N) control strain. 2. N omega-nitro-L-arginine methyl ester was given to GH and N groups in their drinking water from age 7-10 weeks (10 mg/kg per day for week 1 and 2 and then 5 mg/kg per day for week 3). Tailcuff blood pressure (BP) was measured weekly and at the end of the experiment the mesentery was fixed by perfusion, second order branches of the mesenteric artery were embedded in Technovit and stained sections were used to quantify the structure of the mesenteric resistance arteries (MRA). The heart was removed and weighed for determination of left ventricular (LV) mass. 3. In GH rats, BP and LV mass were significantly raised by L-NAME, while in N rats L-NAME treatment significantly elevated BP, but had no effect on LV mass. 4. In GH rats, the media width was significantly increased by L-NAME treatment (P < 0.01); lumen diameter remained unchanged. Thus, the ratio of media width/lumen diameter (M/L) was significantly increased by exacerbation of the hypertrophic outward remodelling characteristic of the GH strain. There were no significant changes in the M/L ratio in L-NAME-treated N rats. 5. Thus, in the GH strain, cardiovascular structure is more sensitive to NOS inhibition than either its N control strain or (on evidence from the literature) the spontaneously hypertensive rat strain.
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; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects*; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D014655:Vascular Resistance / Q000187:drug effects
D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester