title: Remodelling of resistance arteries in genetically hypertensive rats by treatment with valsartan, an angiotensin II receptor antagonist.
abstract: 1. In the present study, New Zealand genetically hypertensive (GH) rats were treated with valsartan, a specific angiotensin II (AT1) receptor antagonist, to measure the effects on blood pressure (BP), cardiac hypertrophy and the structure of resistance arteries. Normotensive (N) rats were used as controls. 2. Valsartan (val) was given to GH rats at three different doses (10, 3 or 0.3 mg/kg per day, via osmotic mini-pumps implanted i.p.) from age 4-10 weeks. Untreated GH (mini-pump + vehicle) and N rats (mini-pump + vehicle) were used as controls. BP was measured weekly and at the end of the experiment, left ventricular (LV) mass was recorded and the structure of mesenteric resistance arteries (MRA) was determined using stereological methods. 3. BP fell in a dose-dependent fashion, being reduced to normotensive levels by 10 mg/kg; LV mass was significantly reduced (P < 0.0001) to below normotensive values in the GH group given 10 mg/kg val and significantly reduced (P < 0.001), although not normalized, in the other two treatment groups. 4. In MRA, the media/lumen (M/L) ratio was reduced by val according to dose level, to below normotensive values in GHval10, and to levels not different from normotensive values in the GHval3 and GHval0.3 groups. 5. The hypertrophy of smooth muscle cells in GH rats was reduced with val treatment at all doses. 6. Reversal of cardiac and vascular hypertrophy occurred even when BP was not reduced to normotensive levels, indicating an effect on vessel growth but without any retardation of body growth. 7. These results suggest that the vascular structural changes seen after val and angiotensin converting enzyme inhibitor treatment are probably due to the blocking of angiotensin rather than any bradykinin effect.
authors.affiliation: Department of Pharmacology, University of Otago Medical School, Dunedin, New Zealand.
authors.forename: J M
authors.initials: JM
authors.lastname: Ledingham
authors.forename: R
authors.initials: R
authors.lastname: Laverty
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000473:pathology; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D009389:Neovascularization, Pathologic / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism; D013152:Splanchnic Circulation / Q000187:drug effects; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D014633:Valine