title: In vivo expression of angiotensin-(1-7) lowers blood pressure and improves baroreflex function in transgenic (mRen2)27 rats.
abstract: Transgenic (mRen2)27 rats are hypertensive with impaired baroreflex sensitivity for control of heart rate compared with Hannover Sprague-Dawley rats. We assessed blood pressure and baroreflex function in male hemizygous (mRen2)27 rats (30-40 weeks of age) instrumented for arterial pressure recordings and receiving into the cisterna magna either an Ang-(1-7) fusion protein or a control fusion protein (CTL-FP). The maximum reduction in mean arterial pressure achieved was -38 ± 7 mm Hg on day 3, accompanied by a 55% enhancement in baroreflex sensitivity in Ang-(1-7) fusion protein-treated rats. Both the high-frequency alpha index (HF-α) and heart rate variability increased, suggesting increased parasympathetic tone for cardiac control. The mRNA levels of several components of the renin-angiotensin system in the dorsal medulla were markedly reduced including renin (-80%), neprilysin (-40%), and the AT1a receptor (-40%). However, there was a 2-fold to 3-fold increase in the mRNA levels of the phosphatases PTP-1b and dual-specificity phosphatase 1 in the medulla of Ang-(1-7) fusion protein-treated rats. Our finding that replacement of Ang-(1-7) in the brain of (mRen2)27 rats reverses in part the hypertension and baroreflex impairment is consistent with a functional deficit of Ang-(1-7) in this hypertensive strain. We conclude that the increased mRNA expression of phosphatases known to counteract the phosphoinositol 3 kinase and mitogen-activated protein kinases, and the reduction of renin and AT1a receptor mRNA levels may contribute to the reduction in arterial pressure and improvement in baroreflex sensitivity in response to Ang-(1-7).
authors.affiliation: Radiation Oncology Department †Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1032, USA.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Garcia-Espinosa
authors.forename: Hossam A
authors.initials: HA
authors.lastname: Shaltout
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Gallagher
authors.forename: Mark C
authors.initials: MC
authors.lastname: Chappell
authors.forename: Debra I
authors.initials: DI
authors.lastname: Diz
mesh_terms: D000803:Angiotensin I / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D062186:Arterial Pressure / Q000235:genetics; D001341:Autonomic Nervous System / Q000503:physiopathology; D017704:Baroreflex / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006339:Heart Rate; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D007267:Injections; D008297:Male; D051379:Mice; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000235:genetics; D013997:Time Factors
chemical_list: C544067:Agtr1a protein, rat; D010446:Peptide Fragments; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; C473112:Ren2 protein, mouse; D000803:Angiotensin I; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516610:Ptpn1 protein, rat; D012083:Renin; D015260:Neprilysin; C118790:angiotensin I (1-7)