title: Origin of the Y chromosome influences intrarenal vascular responsiveness to angiotensin I and angiotensin (1-7) in stroke-prone spontaneously hypertensive rats.
abstract: The lineage of the Y chromosome accounts for up to 15 to 20 mm Hg in arterial pressure. Genes located on the Y chromosome from the spontaneously hypertensive rat (SHR) are associated with the renin-angiotensin system. Given the important role of the renin-angiotensin system in the renal regulation of fluid homeostasis and arterial pressure, we hypothesized that the origin of the Y chromosome influences arterial pressure via interaction between the intrarenal vasculature and the renin-angiotensin system. Sixteen-week-old normotensive rats (Wistar Kyoto [WKY]), spontaneously hypertensive stroke-prone rat (SHRSP), and 2 reciprocal Y consomic rat strains, 1 comprising the WKY autosomes and X chromosome with the Y chromosome from the hypertensive rat strain (WKY.SPGlaY) and vice versa (SP.WKYGlaY), were examined. SP.WKYGlaY had lower systolic blood pressure than SHRSP (195±5 versus 227±8 mm Hg; P<0.03), whereas WKY.SPGlaY had higher systolic blood pressure compared with WKY (157±3 versus 148±3 mm Hg; P<0.05), measured by radiotelemetry. Compared with WKY rats, SHRSP had higher plasma angiotensin(1-7) (Ang (1-7)):Ang II ratio (WKY: 0.13±0.01 versus SHRSP: 1.33±0.4; P<0.005), greater angiotensin II receptor type 2 and Mas receptor mRNA expression, and a blunted renal constrictor response to intrarenal Ang I and Ang(1-7) infusions. Introgression of the normotensive Y chromosome into the SHRSP background (SP.WKYGlaY) restored responses in the SHRSP to WKY levels, evidenced by a reduction in plasma Ang(1-7):Ang II ratio (SP.WKYGlaY: 0.24±0.02; P<0.01), angiotensin II receptor type 2, and Mas receptor mRNA expression and an increased vasoconstrictor response to intrarenal Ang I and Ang(1-7) infusion. This study demonstrates that the origin of the Y chromosome significantly impacts the renal vascular responsiveness and therefore may influence the long-term renal regulation of blood pressure.
authors.affiliation: From the Director's Research Group (A.K.S., G.L.J.), Department of Vascular Pharmacology (A.K.S., K.L.A., J.P.F.C.-D.), Department of Neuropharmacology (G.A.H.), and Department of Diabetic Complications (M.C.T.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; and Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., M.W.M., A.F.D.). amanda.sampson@bakeridi.edu.au.
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Sampson
authors.affiliation: From the Director's Research Group (A.K.S., G.L.J.), Department of Vascular Pharmacology (A.K.S., K.L.A., J.P.F.C.-D.), Department of Neuropharmacology (G.A.H.), and Department of Diabetic Complications (M.C.T.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; and Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., M.W.M., A.F.D.).
authors.forename: Karen L
authors.initials: KL
authors.lastname: Andrews
authors.affiliation: From the Director's Research Group (A.K.S., G.L.J.), Department of Vascular Pharmacology (A.K.S., K.L.A., J.P.F.C.-D.), Department of Neuropharmacology (G.A.H.), and Department of Diabetic Complications (M.C.T.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; and Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., M.W.M., A.F.D.).
authors.forename: Delyth
authors.initials: D
authors.lastname: Graham
authors.affiliation: From the Director's Research Group (A.K.S., G.L.J.), Department of Vascular Pharmacology (A.K.S., K.L.A., J.P.F.C.-D.), Department of Neuropharmacology (G.A.H.), and Department of Diabetic Complications (M.C.T.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; and Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., M.W.M., A.F.D.).
authors.forename: Martin W
authors.initials: MW
authors.lastname: McBride
authors.affiliation: From the Director's Research Group (A.K.S., G.L.J.), Department of Vascular Pharmacology (A.K.S., K.L.A., J.P.F.C.-D.), Department of Neuropharmacology (G.A.H.), and Department of Diabetic Complications (M.C.T.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; and Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., M.W.M., A.F.D.).
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Head
authors.affiliation: From the Director's Research Group (A.K.S., G.L.J.), Department of Vascular Pharmacology (A.K.S., K.L.A., J.P.F.C.-D.), Department of Neuropharmacology (G.A.H.), and Department of Diabetic Complications (M.C.T.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; and Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., M.W.M., A.F.D.).
authors.forename: Merlin C
authors.initials: MC
authors.lastname: Thomas
authors.affiliation: From the Director's Research Group (A.K.S., G.L.J.), Department of Vascular Pharmacology (A.K.S., K.L.A., J.P.F.C.-D.), Department of Neuropharmacology (G.A.H.), and Department of Diabetic Complications (M.C.T.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; and Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., M.W.M., A.F.D.).
authors.forename: Jaye P F
authors.initials: JP
authors.lastname: Chin-Dusting
authors.affiliation: From the Director's Research Group (A.K.S., G.L.J.), Department of Vascular Pharmacology (A.K.S., K.L.A., J.P.F.C.-D.), Department of Neuropharmacology (G.A.H.), and Department of Diabetic Complications (M.C.T.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; and Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., M.W.M., A.F.D.).
authors.forename: Anna F
authors.initials: AF
authors.lastname: Dominiczak
authors.affiliation: From the Director's Research Group (A.K.S., G.L.J.), Department of Vascular Pharmacology (A.K.S., K.L.A., J.P.F.C.-D.), Department of Neuropharmacology (G.A.H.), and Department of Diabetic Complications (M.C.T.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; and Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., M.W.M., A.F.D.).
authors.forename: Garry L
authors.initials: GL
authors.lastname: Jennings
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012077:Renal Artery / Q000187:drug effects / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents; D014998:Y Chromosome / Q000235:genetics*
chemical_list: D010446:Peptide Fragments; D014665:Vasodilator Agents; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: gene expression; hypertension; rats; rats, inbred SHR; renal circulation; renin-angiotensin system