Impaired myogenic response of the afferent arteriole contributes to the increased susceptibility to renal disease in Milan normotensive rats

Ying Ge; Fan Fan; Sean P. Didion; Richard J. Roman

doi:10.14814/phy2.13089

Impaired myogenic response of the afferent arteriole contributes to the increased susceptibility to renal disease in Milan normotensive rats

Ying Ge, Fan Fan, Sean P. Didion, Richard J. Roman

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Milan normotensive (MNS) rats are more susceptible to the development of renal disease than Milan hypertensive (MHS) rats, but the genes and pathways involved are unknown. This study compared the myogenic response of isolated perfused afferent arterioles (Af-Art) and autoregulation of renal blood flow (RBF) and glomerular capillary pressure (Pgc) in 6–9-week-old MNS and MHS rats. The diameter of the Af-Art of MHS rats decreased significantly from 14.3 ± 0.5 to 11.5 ± 0.6 μm when perfusion pressure was elevated from 60 to 120 mmHg. In contrast, the diameter of Af-Art of MNS rats did not decrease. RBF was well autoregulated in MHS rats, but it increased by 26% in MNS rats. Pgc rose by 11 mmHg when renal perfusion pressure (RPP) was increased from 100 to 140 mmHg in MNS but not in MHS rats. Protein excretion increased from 10 ± 1 to 245 ± 36 mg/day in MNS rats as they aged from 3 to 11 months but it did not increase in MHS rats. We also compared the development of proteinuria in MNS and MHS rats following the induction of diabetes with streptozotocin. Protein excretion rose from 16 ± 3 to 234 ± 43 mg/day in MNS rats, but it remained unaltered in MHS rats. These data indicate that the myogenic response of the Af-art is impaired in MNS rats and increased transmission of pressure to the glomerulus may contribute to renal injury in MNS rats similar to what is seen in fawn-hooded hypertensive and Dahl salt-sensitive rats.

Original language	English (US)
Article number	e13089
Journal	Physiological reports
Volume	5
Issue number	3
DOIs	https://doi.org/10.14814/phy2.13089
State	Published - Feb 1 2017
Externally published	Yes

Keywords

Chronic kidney disease
diabetic nephropathy
glomerulus
renal hemodynamics

ASJC Scopus subject areas

Physiology
Physiology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.14814/phy2.13089

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title = "Impaired myogenic response of the afferent arteriole contributes to the increased susceptibility to renal disease in Milan normotensive rats",

abstract = "Milan normotensive (MNS) rats are more susceptible to the development of renal disease than Milan hypertensive (MHS) rats, but the genes and pathways involved are unknown. This study compared the myogenic response of isolated perfused afferent arterioles (Af-Art) and autoregulation of renal blood flow (RBF) and glomerular capillary pressure (Pgc) in 6–9-week-old MNS and MHS rats. The diameter of the Af-Art of MHS rats decreased significantly from 14.3 ± 0.5 to 11.5 ± 0.6 μm when perfusion pressure was elevated from 60 to 120 mmHg. In contrast, the diameter of Af-Art of MNS rats did not decrease. RBF was well autoregulated in MHS rats, but it increased by 26% in MNS rats. Pgc rose by 11 mmHg when renal perfusion pressure (RPP) was increased from 100 to 140 mmHg in MNS but not in MHS rats. Protein excretion increased from 10 ± 1 to 245 ± 36 mg/day in MNS rats as they aged from 3 to 11 months but it did not increase in MHS rats. We also compared the development of proteinuria in MNS and MHS rats following the induction of diabetes with streptozotocin. Protein excretion rose from 16 ± 3 to 234 ± 43 mg/day in MNS rats, but it remained unaltered in MHS rats. These data indicate that the myogenic response of the Af-art is impaired in MNS rats and increased transmission of pressure to the glomerulus may contribute to renal injury in MNS rats similar to what is seen in fawn-hooded hypertensive and Dahl salt-sensitive rats.",

keywords = "Chronic kidney disease, diabetic nephropathy, glomerulus, renal hemodynamics",

author = "Ying Ge and Fan Fan and Didion, {Sean P.} and Roman, {Richard J.}",

note = "Funding Information: Funding Information This work was supported in part by grants HL36279 and DK104184 (Roman), AG050049 (Fan), P20GM104357 (cores B and C-Roman; Pilot-Fan) from the National Institutes of Health and 16GRNT31200036 (Fan) from American Heart Association. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. The authors thank Wenjie Wu who provided technical assistance with the breeding and maintenance of the animal colonies. Publisher Copyright: {\textcopyright} 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.",

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doi = "10.14814/phy2.13089",

language = "English (US)",

volume = "5",

journal = "Physiological reports",

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TY - JOUR

T1 - Impaired myogenic response of the afferent arteriole contributes to the increased susceptibility to renal disease in Milan normotensive rats

AU - Ge, Ying

AU - Fan, Fan

AU - Didion, Sean P.

AU - Roman, Richard J.

N1 - Funding Information: Funding Information This work was supported in part by grants HL36279 and DK104184 (Roman), AG050049 (Fan), P20GM104357 (cores B and C-Roman; Pilot-Fan) from the National Institutes of Health and 16GRNT31200036 (Fan) from American Heart Association. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. The authors thank Wenjie Wu who provided technical assistance with the breeding and maintenance of the animal colonies. Publisher Copyright: © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Milan normotensive (MNS) rats are more susceptible to the development of renal disease than Milan hypertensive (MHS) rats, but the genes and pathways involved are unknown. This study compared the myogenic response of isolated perfused afferent arterioles (Af-Art) and autoregulation of renal blood flow (RBF) and glomerular capillary pressure (Pgc) in 6–9-week-old MNS and MHS rats. The diameter of the Af-Art of MHS rats decreased significantly from 14.3 ± 0.5 to 11.5 ± 0.6 μm when perfusion pressure was elevated from 60 to 120 mmHg. In contrast, the diameter of Af-Art of MNS rats did not decrease. RBF was well autoregulated in MHS rats, but it increased by 26% in MNS rats. Pgc rose by 11 mmHg when renal perfusion pressure (RPP) was increased from 100 to 140 mmHg in MNS but not in MHS rats. Protein excretion increased from 10 ± 1 to 245 ± 36 mg/day in MNS rats as they aged from 3 to 11 months but it did not increase in MHS rats. We also compared the development of proteinuria in MNS and MHS rats following the induction of diabetes with streptozotocin. Protein excretion rose from 16 ± 3 to 234 ± 43 mg/day in MNS rats, but it remained unaltered in MHS rats. These data indicate that the myogenic response of the Af-art is impaired in MNS rats and increased transmission of pressure to the glomerulus may contribute to renal injury in MNS rats similar to what is seen in fawn-hooded hypertensive and Dahl salt-sensitive rats.

AB - Milan normotensive (MNS) rats are more susceptible to the development of renal disease than Milan hypertensive (MHS) rats, but the genes and pathways involved are unknown. This study compared the myogenic response of isolated perfused afferent arterioles (Af-Art) and autoregulation of renal blood flow (RBF) and glomerular capillary pressure (Pgc) in 6–9-week-old MNS and MHS rats. The diameter of the Af-Art of MHS rats decreased significantly from 14.3 ± 0.5 to 11.5 ± 0.6 μm when perfusion pressure was elevated from 60 to 120 mmHg. In contrast, the diameter of Af-Art of MNS rats did not decrease. RBF was well autoregulated in MHS rats, but it increased by 26% in MNS rats. Pgc rose by 11 mmHg when renal perfusion pressure (RPP) was increased from 100 to 140 mmHg in MNS but not in MHS rats. Protein excretion increased from 10 ± 1 to 245 ± 36 mg/day in MNS rats as they aged from 3 to 11 months but it did not increase in MHS rats. We also compared the development of proteinuria in MNS and MHS rats following the induction of diabetes with streptozotocin. Protein excretion rose from 16 ± 3 to 234 ± 43 mg/day in MNS rats, but it remained unaltered in MHS rats. These data indicate that the myogenic response of the Af-art is impaired in MNS rats and increased transmission of pressure to the glomerulus may contribute to renal injury in MNS rats similar to what is seen in fawn-hooded hypertensive and Dahl salt-sensitive rats.

KW - Chronic kidney disease

KW - diabetic nephropathy

KW - glomerulus

KW - renal hemodynamics

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DO - 10.14814/phy2.13089

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JO - Physiological reports

JF - Physiological reports

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M1 - e13089

ER -

Impaired myogenic response of the afferent arteriole contributes to the increased susceptibility to renal disease in Milan normotensive rats

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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