Origin of the Y chromosome influences intrarenal vascular responsiveness to angiotensin I and angiotensin (1-7) in stroke-prone spontaneously hypertensive rats

Amanda K. Sampson; Karen L. Andrews; Delyth Graham; Martin W. McBride; Geoffrey A. Head; Merlin C. Thomas; Jaye P F Chin-Dusting; Anna F. Dominiczak; Garry L. Jennings

doi:10.1161/HYPERTENSIONAHA.114.03756

Origin of the Y chromosome influences intrarenal vascular responsiveness to angiotensin I and angiotensin (1-7) in stroke-prone spontaneously hypertensive rats

Amanda K. Sampson, Karen L. Andrews, Delyth Graham, Martin W. McBride, Geoffrey A. Head, Merlin C. Thomas, Jaye P F Chin-Dusting, Anna F. Dominiczak, Garry L. Jennings

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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.WKY_GlaY), were examined. SP.WKY_GlaY had lower systolic blood pressure than SHRSP (195±5 versus 227±8 mm Hg; P<0.03), whereas WKY.SP_GlaY 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.WKY_GlaY) restored responses in the SHRSP to WKY levels, evidenced by a reduction in plasma Ang(1-7):Ang II ratio (SP.WKY_GlaY: 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.

Original language	English
Pages (from-to)	1376-1383
Number of pages	8
Journal	Hypertension
Volume	64
Issue number	6
DOIs	https://doi.org/10.1161/HYPERTENSIONAHA.114.03756
Publication status	Published - 2014
Externally published	Yes

Keywords

Gene expression
Hypertension
Inbred SHR
Rats
Renal circulation
Renin-angiotensin system

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Sampson, A. K., Andrews, K. L., Graham, D., McBride, M. W., Head, G. A., Thomas, M. C., Chin-Dusting, J. P. F., Dominiczak, A. F., & Jennings, G. L. (2014). Origin of the Y chromosome influences intrarenal vascular responsiveness to angiotensin I and angiotensin (1-7) in stroke-prone spontaneously hypertensive rats. Hypertension, 64(6), 1376-1383. https://doi.org/10.1161/HYPERTENSIONAHA.114.03756

@article{b74cdd8d56434418bd4a42c5cfddcb5d,

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.",

keywords = "Gene expression, Hypertension, Inbred SHR, Rats, Renal circulation, Renin-angiotensin system",

author = "Sampson, {Amanda K.} and Andrews, {Karen L.} and Delyth Graham and McBride, {Martin W.} and Head, {Geoffrey A.} and Thomas, {Merlin C.} and Chin-Dusting, {Jaye P F} and Dominiczak, {Anna F.} and Jennings, {Garry L.}",

year = "2014",

doi = "10.1161/HYPERTENSIONAHA.114.03756",

language = "English",

volume = "64",

pages = "1376--1383",

journal = "Hypertension",

issn = "0194-911X",

publisher = "American Heart Association",

number = "6",

}

Sampson, AK, Andrews, KL, Graham, D, McBride, MW, Head, GA, Thomas, MC, Chin-Dusting, JPF, Dominiczak, AF & Jennings, GL 2014, 'Origin of the Y chromosome influences intrarenal vascular responsiveness to angiotensin I and angiotensin (1-7) in stroke-prone spontaneously hypertensive rats', Hypertension, vol. 64, no. 6, pp. 1376-1383. https://doi.org/10.1161/HYPERTENSIONAHA.114.03756

TY - JOUR

T1 - Origin of the Y chromosome influences intrarenal vascular responsiveness to angiotensin I and angiotensin (1-7) in stroke-prone spontaneously hypertensive rats

AU - Sampson, Amanda K.

AU - Andrews, Karen L.

AU - Graham, Delyth

AU - McBride, Martin W.

AU - Head, Geoffrey A.

AU - Thomas, Merlin C.

AU - Chin-Dusting, Jaye P F

AU - Dominiczak, Anna F.

AU - Jennings, Garry L.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Gene expression

KW - Hypertension

KW - Inbred SHR

KW - Rats

KW - Renal circulation

KW - Renin-angiotensin system

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U2 - 10.1161/HYPERTENSIONAHA.114.03756

DO - 10.1161/HYPERTENSIONAHA.114.03756

M3 - Article

C2 - 25201895

AN - SCOPUS:84922481991

SN - 0194-911X

VL - 64

SP - 1376

EP - 1383

JO - Hypertension

JF - Hypertension

IS - 6

ER -

Origin of the Y chromosome influences intrarenal vascular responsiveness to angiotensin I and angiotensin (1-7) in stroke-prone spontaneously hypertensive rats

Abstract

Keywords

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