title: The effects of perindopril on vascular smooth muscle polyploidy in stroke-prone spontaneously hypertensive rats.
abstract: OBJECTIVE
  To quantify vascular smooth muscle polyploidy and growth kinetics in aortic cells from stroke-prone spontaneously hypertensive rats (SHRSP) and from normotensive Wistar-Kyoto (WKY) rats, and to examine the effects of treatment with the angiotensin converting enzyme (ACE) inhibitor perindopril on these parameters.
  
  
  METHODS
  The following experimental groups were used: young (age < 20 weeks) and old (age > 20 weeks) untreated WKY rats and untreated SHRSP; SHRSP treated with perindopril, and age- and sex-matched control SHRSP; and SHRSP treated with hydralazine and hydrochlorothiazide and age- and sex-matched control SHRSP. The effects of treatment of the SHRSP with perindopril for 30 days on vascular smooth muscle polyploidy and growth kinetics were measured and compared with the effects of equivalent antihypertensive doses of hydralazine and hydrochlorothiazide.
  
  
  METHODS
  Vascular smooth muscle polyploidy was measured using flow-cytometry DNA analysis of freshly harvested cells. Growth curves were performed on cultured aortic cells. Plasma renin activity was measured by an antibody-trapping method, plasma angiotensin II (Ang II) by radioimmunoassay and plasma ACE activity by a colorimetric method. Cardiac hypertrophy was evaluated by measuring the heart weight:body weight and left ventricle + septum weight:body weight ratios.
  
  
  RESULTS
  The SHRSP had markedly and significantly elevated G2 + M phase of the cell cycle. Treatment with perindopril resulted in a significant reduction in polyploidy in the SHRSP, whereas treatment with hydralazine and hydrochlorothiazide had no effect on the percentage of cells in the G2 + M phase of the cell cycle. The regression of polyploidy after treatment with perindopril was associated with a significant reduction in the concentration of Ang II and ACE activity, and with a significant regression of cardiac hypertrophy. Increased mitogenesis of cultured vascular smooth muscle cells from the SHRSP was not altered by treatment with perindopril.
  
  
  CONCLUSIONS
  ACE inhibition reduces vascular smooth muscle polyploidy in large conduit arteries. This type of vascular protection is mediated by the reduced Ang II and possibly by increased kinins level, rather than by the hypotensive effect alone.
authors.affiliation: Department of Medicine and Therapeutics, University of Glasgow, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Devlin
authors.forename: J F
authors.initials: JF
authors.lastname: Gordon
authors.forename: A O
authors.initials: AO
authors.lastname: Davidson
authors.forename: J S
authors.initials: JS
authors.lastname: Clark
authors.forename: C A
authors.initials: CA
authors.lastname: Hamilton
authors.forename: J J
authors.initials: JJ
authors.lastname: Morton
authors.forename: A M
authors.initials: AM
authors.lastname: Campbell
authors.forename: J L
authors.initials: JL
authors.lastname: Reid
authors.forename: A F
authors.initials: AF
authors.lastname: Dominiczak
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000809:Angiotensins / Q000097:blood; D000818:Animals; D001011:Aorta / Q000473:pathology; D001794:Blood Pressure; D002467:Cell Nucleus / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006339:Heart Rate; D006973:Hypertension / Q000378:metabolism / Q000473:pathology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D020913:Perindopril; D011123:Polyploidy; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012083:Renin / Q000097:blood
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D007211:Indoles; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D020913:Perindopril