Rosiglitazone reduces blood pressure in female Dahl salt-sensitive rats

Julio Sartori Valinotti, Marcia R. Venegas-Pont, Babbette B. LaMarca, Damian G. Romero, Licy L. Yanes, Lorraine C. Racusen, Allison V. Jones, Michael J. Ryan, Jane F. Reckelhoff

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Postmenopausal women (PMW) are at greater risk for salt-sensitive hypertension and insulin resistance than premenopausal women. Peroxisome-proliferator-activated receptor-gamma (PPARγ) agonists reduce blood pressure (BP) and insulin resistance in humans. As in PMW, ovariectomy (OVX) increases salt sensitivity of BP and body weight in Dahl salt-sensitive (DS) rats. This study addressed whether rosiglitazone (ROSI), a PPARγ agonist, attenuates salt-sensitive hypertension in intact (INT) and OVX DS rats, and if so, whether insulin resistance, nitric oxide (NO), oxidative stress, and/or renal inflammation were contributing mediators. Telemetric BP was similar in OVX and INT on low salt diet (0.3% NaCl), but was higher in OVX than INT on high salt (8% NaCl). ROSI reduced BP in OVX and INT on both low and high salt diet, but only attenuated salt sensitivity of BP in OVX. Nitrate/nitrite excretion (NOx; index of NO) was similar in INT and OVX on low salt diet, and ROSI increased NOx in both groups. High salt diet increased NOx in all groups but ROSI only increased NOx in OVX rats. OVX females exhibited insulin resistance, increases in body weight, plasma leptin, cholesterol, numbers of renal cortical macrophages, and renal MCP-1 and osteopontin mRNA expression compared to INT. ROSI reduced cholesterol and macrophage infiltration in OVX, but not INT. In summary, PPARγ activation reduces BP in INT and OVX females, but attenuates the salt sensitivity of BP in OVX only, likely due to increases in NO and in part to reductions in renal resident macrophages and inflammation.

Original languageEnglish (US)
Pages (from-to)794-799
Number of pages6
JournalSteroids
Volume75
Issue number11
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

Fingerprint

rosiglitazone
Inbred Dahl Rats
Blood pressure
Rats
Salts
Blood Pressure
Sodium-Restricted Diet
Insulin Resistance
PPAR gamma
Kidney
Nitric Oxide
Nutrition
Macrophages
Insulin
Cholesterol
Body Weight
Hypertension
Inflammation
Osteopontin
Ovariectomy

Keywords

  • Hypertension
  • Inflammation
  • Menopause
  • Ovariectomy
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Pharmacology
  • Endocrinology
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Sartori Valinotti, J., Venegas-Pont, M. R., LaMarca, B. B., Romero, D. G., Yanes, L. L., Racusen, L. C., ... Reckelhoff, J. F. (2010). Rosiglitazone reduces blood pressure in female Dahl salt-sensitive rats. Steroids, 75(11), 794-799. https://doi.org/10.1016/j.steroids.2009.10.010

Rosiglitazone reduces blood pressure in female Dahl salt-sensitive rats. / Sartori Valinotti, Julio; Venegas-Pont, Marcia R.; LaMarca, Babbette B.; Romero, Damian G.; Yanes, Licy L.; Racusen, Lorraine C.; Jones, Allison V.; Ryan, Michael J.; Reckelhoff, Jane F.

In: Steroids, Vol. 75, No. 11, 01.11.2010, p. 794-799.

Research output: Contribution to journalArticle

Sartori Valinotti, J, Venegas-Pont, MR, LaMarca, BB, Romero, DG, Yanes, LL, Racusen, LC, Jones, AV, Ryan, MJ & Reckelhoff, JF 2010, 'Rosiglitazone reduces blood pressure in female Dahl salt-sensitive rats', Steroids, vol. 75, no. 11, pp. 794-799. https://doi.org/10.1016/j.steroids.2009.10.010
Sartori Valinotti J, Venegas-Pont MR, LaMarca BB, Romero DG, Yanes LL, Racusen LC et al. Rosiglitazone reduces blood pressure in female Dahl salt-sensitive rats. Steroids. 2010 Nov 1;75(11):794-799. https://doi.org/10.1016/j.steroids.2009.10.010
Sartori Valinotti, Julio ; Venegas-Pont, Marcia R. ; LaMarca, Babbette B. ; Romero, Damian G. ; Yanes, Licy L. ; Racusen, Lorraine C. ; Jones, Allison V. ; Ryan, Michael J. ; Reckelhoff, Jane F. / Rosiglitazone reduces blood pressure in female Dahl salt-sensitive rats. In: Steroids. 2010 ; Vol. 75, No. 11. pp. 794-799.
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abstract = "Postmenopausal women (PMW) are at greater risk for salt-sensitive hypertension and insulin resistance than premenopausal women. Peroxisome-proliferator-activated receptor-gamma (PPARγ) agonists reduce blood pressure (BP) and insulin resistance in humans. As in PMW, ovariectomy (OVX) increases salt sensitivity of BP and body weight in Dahl salt-sensitive (DS) rats. This study addressed whether rosiglitazone (ROSI), a PPARγ agonist, attenuates salt-sensitive hypertension in intact (INT) and OVX DS rats, and if so, whether insulin resistance, nitric oxide (NO), oxidative stress, and/or renal inflammation were contributing mediators. Telemetric BP was similar in OVX and INT on low salt diet (0.3{\%} NaCl), but was higher in OVX than INT on high salt (8{\%} NaCl). ROSI reduced BP in OVX and INT on both low and high salt diet, but only attenuated salt sensitivity of BP in OVX. Nitrate/nitrite excretion (NOx; index of NO) was similar in INT and OVX on low salt diet, and ROSI increased NOx in both groups. High salt diet increased NOx in all groups but ROSI only increased NOx in OVX rats. OVX females exhibited insulin resistance, increases in body weight, plasma leptin, cholesterol, numbers of renal cortical macrophages, and renal MCP-1 and osteopontin mRNA expression compared to INT. ROSI reduced cholesterol and macrophage infiltration in OVX, but not INT. In summary, PPARγ activation reduces BP in INT and OVX females, but attenuates the salt sensitivity of BP in OVX only, likely due to increases in NO and in part to reductions in renal resident macrophages and inflammation.",
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AU - LaMarca, Babbette B.

AU - Romero, Damian G.

AU - Yanes, Licy L.

AU - Racusen, Lorraine C.

AU - Jones, Allison V.

AU - Ryan, Michael J.

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