Long-term effects of treatment with enalapril on the structure of mesenteric resistance arteries in New Zealand genetically hypertensive rats.
1. New Zealand genetically hypertensive (GH) rats were treated with enalapril (20 mg/kg per day in drinking fluids) from age 4-10 weeks; one group (GHex-enal) was then taken off enalapril and followed for 6 more weeks to see if the drug-induced changes in blood pressure (BP) and structure of mesenteric resistance arteries (MRA) were long lasting once the enalapril was withdrawn. Control groups consisted of untreated GH and their normotensive (N) control strain. 2. Tail-cuff BP in GH treated rats fell significantly to N BP levels during treatment. On cessation of treatment BP rose rapidly. At age 16 weeks BP, although at a hypertensive level (mean +/- s.e.m., GHex-enal, 210.8 +/- 4.7 mmHg), was still significantly below the GH controls (230 +/- 6.9, P < 0.05), but above the N control group (137 +/- 3, P < 0.001). 3. Left ventricular (LV) mass in GH rats was reduced by enalapril to that in N rats; at the end of the subsequent period without treatment it was still significantly lower than the GH control group, but also significantly above the N group (GHex-enal, 255 +/- 6; GH 306 +/- 11; N 179 +/- 3, mg/100 g bodyweight). 4. The large changes in media, lumen and media/lumen ratio seen after 6 weeks of treatment were not sustained over the subsequent non-treatment period. However, values in the GHex-enal group at 16 weeks were closer to those in the N16 control group. 5. The persisting effects on smooth muscle (SM) cell density and SM fraction of the media contributed to an increase in SM cell volume which was significantly greater than the N16 group (P < 0.01). The number of layers of SM in the media was less than in the GH16 control group and not different from the N16 controls. 6. In GH rats the effect of ACEI on PB, LV mass and MRA structure is relatively longlasting once treatment is withdrawn.
Ledingham
J M
JM
Department of Pharmacology, University of Otago Medical School, Dunedin, New Zealand.
Laverty
R
R
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004656:Enalapril / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000473:pathology; D008297:Male; D008638:Mesenteric Arteries / Q000473:pathology*; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D051381:Rats; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril