Remodelling of resistance arteries by treatment with enalapril in the New Zealand genetically hypertensive rat.
1. New Zealand genetically hypertensive (GH) rats were treated with enalapril from the age of 4 to 10 weeks and the effects of treatment on the structure of mesenteric resistance arteries (MRA) was measured by use of stereological analysis of stained sections and by myograph techniques. 2. Tail-cuff blood pressure (BP) was measured weekly and intra-arterial BP recorded just before MRA were either fixed by perfusion or mounted on a myograph. 3. Stereological techniques (Cavalieri and optical dissector) were used to determine media and lumen volume, fraction of smooth muscle (SM) within the media and SM cell density. For MRA mounted on the myograph, lumen diameter, media thickness, active tension and active pressure were recorded. 4. BP was significantly (P < 0.0001) lowered by enalapril throughout the experiment. Intraarterial BP and left ventricular (LV) mass were also significantly lower in the enalapril treated GH rats (P < 0.0001). 5. Stereological measurements showed that enalapril treatment significantly (P < 0.0001) reduced media volume by 50%, doubled lumen volume (P < 0.0001), reduced the fraction of SM in the media (P < 0.04), and had no effect on the number of SM cell layers or on SM cell density. 6. Myograph measurements showed a decrease in the ratio media thickness/lumen diameter which was accompanied by a decrease in maximum active tension and pressure development. 7. In the GH rat early treatment with enalapril causes a true loss of medial tissue that is not simply due to rearrangement of existing media around an enlarged lumen.(ABSTRACT TRUNCATED AT 250 WORDS)
Ledingham
J M
JM
Department of Pharmacology, University of Otago Medical School, Dunedin, New Zealand.
Phelan
E L
EL
Cross
M
M
Laverty
R
R
Millar
J A
JA
D000818:Animals; D004656:Enalapril / Q000627:therapeutic use*; D006973:Hypertension / Q000235:genetics* / Q000517:prevention & control*; D008638:Mesenteric Arteries / Q000002:abnormalities* / Q000033:anatomy & histology / Q000187:drug effects*; D009213:Myography; D051381:Rats; D011918:Rats, Inbred SHR; D014655:Vascular Resistance / Q000187:drug effects*
D004656:Enalapril