Preserved regulation of renal perfusion pressure by small and intermediate conductance K<inf>Ca</inf> channels in hypertensive mice with or without renal failure

Ludovic Waeckel, Florence Bertin, Nicolas Clavreul, Thibaut Damery, Ralf Köhler, Jérôme Paysant, Patricia Sansilvestri-Morel, Serge Simonet, Christine Vayssettes-Courchay, Heike Wulff, Tony J. Verbeuren, Michel Félétou

Research output: Contribution to journalArticle

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Abstract

The purpose of this study was to assess, in the murine kidney, the mechanisms underlying the endothelium-dependent control of vascular tone and whether or not, in a severe model of hypertension and renal failure, K<inf>Ca</inf> channels contribute to its regulation. Wild-type (BL) and double-transgenic female mice expressing human angiotensinogen and renin (AR) genes received either control or a high-salt diet associated to a nitric oxide (NO) synthase inhibitor treatment (BLSL and ARSL). Changes in renal perfusion pressure (RPP) were measured in isolated perfused kidneys. BLSL and AR were moderately hypertensive without kidney disease while ARSL developed severe hypertension and renal failure. In the four groups, methacholine induced biphasic endothelium-dependent responses, a transient decrease in RPP followed by a cyclooxygenase-dependent increase in RPP. In the presence or not of indomethacin, the vasodilatations were poorly sensitive to NO synthase inhibition. However, in the presence of cyclooxygenase and NO synthase inhibitors, apamin, and/or TRAM-34, blockers of K<inf>Ca</inf>2.3 and K<inf>Ca</inf>3.1, respectively, abolished the decrease in RPP in response to either methacholine or the two activators of K<inf>Ca</inf>2.3/K<inf>Ca</inf>3.1, NS309, and SKA-31. Thus, K<inf>Ca</inf>2/3 channels play a major role in the regulation of murine kidney perfusion and this mechanism is maintained in hypertension, even when severe and associated with kidney damage.

Original languageEnglish (US)
Pages (from-to)817-831
Number of pages15
JournalPflugers Archiv European Journal of Physiology
Volume467
Issue number4
DOIs
StatePublished - 2015

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Renal Insufficiency
Perfusion
Nitric Oxide Synthase
Kidney
Pressure
Angiotensinogen
Methacholine Chloride
Prostaglandin-Endoperoxide Synthases
Renin
Apamin
Nutrition
Hypertension
Indomethacin
Endothelium
Salts
Genes
Kidney Diseases
Vasodilation
Transgenic Mice
Blood Vessels

Keywords

  • Calcium-activated potassium channels
  • Endothelium-dependent hyperpolarization
  • Endothelium-dependent vasodilatation
  • Hypertension
  • Kidney disease
  • SKA-31

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

Cite this

Preserved regulation of renal perfusion pressure by small and intermediate conductance K<inf>Ca</inf> channels in hypertensive mice with or without renal failure. / Waeckel, Ludovic; Bertin, Florence; Clavreul, Nicolas; Damery, Thibaut; Köhler, Ralf; Paysant, Jérôme; Sansilvestri-Morel, Patricia; Simonet, Serge; Vayssettes-Courchay, Christine; Wulff, Heike; Verbeuren, Tony J.; Félétou, Michel.

In: Pflugers Archiv European Journal of Physiology, Vol. 467, No. 4, 2015, p. 817-831.

Research output: Contribution to journalArticle

Waeckel, L, Bertin, F, Clavreul, N, Damery, T, Köhler, R, Paysant, J, Sansilvestri-Morel, P, Simonet, S, Vayssettes-Courchay, C, Wulff, H, Verbeuren, TJ & Félétou, M 2015, 'Preserved regulation of renal perfusion pressure by small and intermediate conductance K<inf>Ca</inf> channels in hypertensive mice with or without renal failure', Pflugers Archiv European Journal of Physiology, vol. 467, no. 4, pp. 817-831. https://doi.org/10.1007/s00424-014-1542-y
Waeckel, Ludovic ; Bertin, Florence ; Clavreul, Nicolas ; Damery, Thibaut ; Köhler, Ralf ; Paysant, Jérôme ; Sansilvestri-Morel, Patricia ; Simonet, Serge ; Vayssettes-Courchay, Christine ; Wulff, Heike ; Verbeuren, Tony J. ; Félétou, Michel. / Preserved regulation of renal perfusion pressure by small and intermediate conductance K<inf>Ca</inf> channels in hypertensive mice with or without renal failure. In: Pflugers Archiv European Journal of Physiology. 2015 ; Vol. 467, No. 4. pp. 817-831.
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AU - Bertin, Florence

AU - Clavreul, Nicolas

AU - Damery, Thibaut

AU - Köhler, Ralf

AU - Paysant, Jérôme

AU - Sansilvestri-Morel, Patricia

AU - Simonet, Serge

AU - Vayssettes-Courchay, Christine

AU - Wulff, Heike

AU - Verbeuren, Tony J.

AU - Félétou, Michel

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N2 - The purpose of this study was to assess, in the murine kidney, the mechanisms underlying the endothelium-dependent control of vascular tone and whether or not, in a severe model of hypertension and renal failure, KCa channels contribute to its regulation. Wild-type (BL) and double-transgenic female mice expressing human angiotensinogen and renin (AR) genes received either control or a high-salt diet associated to a nitric oxide (NO) synthase inhibitor treatment (BLSL and ARSL). Changes in renal perfusion pressure (RPP) were measured in isolated perfused kidneys. BLSL and AR were moderately hypertensive without kidney disease while ARSL developed severe hypertension and renal failure. In the four groups, methacholine induced biphasic endothelium-dependent responses, a transient decrease in RPP followed by a cyclooxygenase-dependent increase in RPP. In the presence or not of indomethacin, the vasodilatations were poorly sensitive to NO synthase inhibition. However, in the presence of cyclooxygenase and NO synthase inhibitors, apamin, and/or TRAM-34, blockers of KCa2.3 and KCa3.1, respectively, abolished the decrease in RPP in response to either methacholine or the two activators of KCa2.3/KCa3.1, NS309, and SKA-31. Thus, KCa2/3 channels play a major role in the regulation of murine kidney perfusion and this mechanism is maintained in hypertension, even when severe and associated with kidney damage.

AB - The purpose of this study was to assess, in the murine kidney, the mechanisms underlying the endothelium-dependent control of vascular tone and whether or not, in a severe model of hypertension and renal failure, KCa channels contribute to its regulation. Wild-type (BL) and double-transgenic female mice expressing human angiotensinogen and renin (AR) genes received either control or a high-salt diet associated to a nitric oxide (NO) synthase inhibitor treatment (BLSL and ARSL). Changes in renal perfusion pressure (RPP) were measured in isolated perfused kidneys. BLSL and AR were moderately hypertensive without kidney disease while ARSL developed severe hypertension and renal failure. In the four groups, methacholine induced biphasic endothelium-dependent responses, a transient decrease in RPP followed by a cyclooxygenase-dependent increase in RPP. In the presence or not of indomethacin, the vasodilatations were poorly sensitive to NO synthase inhibition. However, in the presence of cyclooxygenase and NO synthase inhibitors, apamin, and/or TRAM-34, blockers of KCa2.3 and KCa3.1, respectively, abolished the decrease in RPP in response to either methacholine or the two activators of KCa2.3/KCa3.1, NS309, and SKA-31. Thus, KCa2/3 channels play a major role in the regulation of murine kidney perfusion and this mechanism is maintained in hypertension, even when severe and associated with kidney damage.

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