title: Involvement of Ras-regulated myosin light chain phosphorylation in the captopril effects in spontaneously hypertensive rats.
abstract: BACKGROUND
  Early treatment with captopril prevents the development of hypertension by inhibiting the generation of angiotensin II and smooth muscle contraction. Although smooth muscle contraction is regulated by myosin light chain phosphorylation (MLC-P), the role of MLC-P in captopril effects in hypertension has not been described. Therefore, we treated spontaneously hypertensive rats (SHR) with captopril and investigated the effects of this agent on downstream signaling.
  
  
  METHODS
  Male SHR (n = 12) were treated with captopril (3.7 mmol/L in drinking water) beginning in utero and continuing up to 12 weeks of age. Age- and sex-matched untreated SHR and Wistar-Kyoto (WKY) rats were used as controls. Rats were split into three subgroups and were sacrificed at 12, 18, or 24 weeks of age. Systolic blood pressure, left ventricular weight, and body weight were measured. Mesenteric arteries were removed for histologic and biochemical studies.
  
  
  RESULTS
  At 12 weeks, captopril significantly decreased systolic blood pressure (from 198 +/- 10 to 125+/-16 mm Hg), reduced left ventricular weight-to-body weight ratios (from 2.94 +/- 0.06 to 2.17 +/- 0.08 mg/g), and prevented vascular remodeling in mesenteric arteries in SHR. Ras expression, extracellular receptor kinase phosphorylation (ERK-P), myosin light chain kinase (MLCK) expression, and MLC-P were all significantly increased in mesenteric arteries in untreated SHR compared with WKY rats. Early captopril treatment in SHR significantly inhibited Ras and MLCK expression at all ages and decreased ERK-P and MLC-P at 12 and 18 weeks in mesenteric arteries.
  
  
  CONCLUSIONS
  These data demonstrate that the antihypertensive effects of captopril are correlated with inhibition of Ras-regulated ERK activation, MLCK expression, and MLC-P.
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Wen-Yang
authors.initials: WY
authors.lastname: Hu
authors.forename: Yoo-Jeong
authors.initials: YJ
authors.lastname: Han
authors.forename: Lian-Zhi
authors.initials: LZ
authors.lastname: Gu
authors.forename: Mariann
authors.initials: M
authors.lastname: Piano
authors.forename: Primal
authors.initials: P
authors.lastname: de Lanerolle
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D002216:Captopril / Q000627:therapeutic use; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011918:Rats, Inbred SHR; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D018994:Myosin Light Chains; D000804:Angiotensin II; D002216:Captopril; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins