Effects of calcium channel blockers on “dynamic” and “steady-state step” renal autoregulation

Griffin, Karen A.; Hacıoğlu, Rıfat; Abu-Amarah, Isam; Loutzenhiser, Rodger; Williamson, G.A.; Bidani, A.

doi:10.1152/ajprenal.00401.2003

Cited by 47 publications

(84 citation statements)

References 43 publications

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“…The myogenic response is much faster, with a natural frequency of 0.1-0.2 Hz in the anaesthetized rats and 0.2-0.3 Hz in conscious animals (2,32,36,38,56,76,122,165,166). Essentially similar data regarding the kinetics of these mechanisms have been obtained through analyses of RBF responses to step changes in BP (84,85,102,175).…”

Section: Bp Variability and The Requirements For Protection Vs Regulmentioning

confidence: 74%

“…Dynamic autoregulatory studies, employing transfer function and frequency domain analyses, have revealed the natural frequency of the TGF mechanism in the rat to be in the range of 0.05 Hz (2,32,36,38,56,76,122,165,166). The myogenic response is much faster, with a natural frequency of 0.1-0.2 Hz in the anaesthetized rats and 0.2-0.3 Hz in conscious animals (2,32,36,38,56,76,122,165,166).…”

Section: Bp Variability and The Requirements For Protection Vs Regulmentioning

confidence: 99%

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Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms

Loutzenhiser

Griffin²,

Bidani³

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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244

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dani. Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms. Am J Physiol Regul Integr Comp Physiol 290: R1153-R1167, 2006. doi:10.1152/ajpregu.00402.2005.-When the kidney is subjected to acute increases in blood pressure (BP), renal blood flow (RBF) and glomerular filtration rate (GFR) are observed to remain relatively constant. Two mechanisms, tubuloglomerular feedback (TGF) and the myogenic response, are thought to act in concert to achieve a precise moment-by-moment regulation of GFR and distal salt delivery. The current view is that this mechanism insulates renal excretory function from fluctuations in BP. Indeed, the concept that renal autoregulation is necessary for normal renal function and volume homeostasis has long been a cornerstone of renal physiology. This article presents a very different view, at least regarding the myogenic component of this response. We suggest that its primary purpose is to protect the kidney against the damaging effects of hypertension. The arguments advanced take into consideration the unique properties of the afferent arteriolar myogenic response that allow it to protect against the oscillating systolic pressure and the accruing evidence that when this response is impaired, the primary consequence is not a disturbed volume homeostasis but rather an increased susceptibility to hypertensive injury. It is suggested that redundant and compensatory mechanisms achieve volume regulation, despite considerable fluctuations in distal delivery, and the assumed moment-by-moment regulation of renal hemodynamics is questioned. Evidence is presented suggesting that additional mechanisms exist to maintain ambient levels of RBF and GFR within normal range, despite chronic alterations in BP and severely impaired acute responses to pressure. Finally, the implications of this new perspective on the divergent roles of the myogenic response to pressure vs. the TGF response to changes in distal delivery are considered, and it is proposed that in addition to TGF-induced vasoconstriction, vasodepressor responses to reduced distal delivery may play a critical role in modulating afferent arteriolar reactivity to integrate the regulatory and protective functions of the renal microvasculature. renal microcirculation; afferent arteriole; myogenic; tubuloglomerular feedback ONE OF THE MOST STRIKING CHARACTERISTICS of the renal circulation is the ability of the kidney to maintain a constant renal blood flow (RBF) and glomerular filtration rate (GFR) as renal perfusion pressure is altered. The dual regulation of both RBF and GFR is achieved by proportionate changes in the preglomerular resistance and is believed to be mediated by two mechanisms, tubuloglomerular feedback (TGF) and the renal myogenic response. TGF involves a flow-dependent signal that is sensed at the macula densa and alters tone in the adjacent segment of the afferent arteriole via a mechanism that remains controversial but likely involves adenosine and/or ATP (30,80,144). The myo...

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Section: Bp Variability and The Requirements For Protection Vs Regulmentioning

confidence: 74%

Section: Bp Variability and The Requirements For Protection Vs Regulmentioning

confidence: 99%

Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms

Loutzenhiser

Griffin²,

Bidani³

2006

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

238

244

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“…[74][75][76][77] Recently T-type channels have also been implicated in the myogenic response of several vascular beds although some studies show that the influence of T-type channels on the myogenic response is more pronounced in the lower pressure range where the VSMC are less depolarized. 46,78,79 In the renal vascular bed inhibition of T-type channels reduce autoregulation, 80,81 but whether this effect is caused by an attenuation of the myogenic response alone or also affects the TGF is unknown. Both mechanisms affect resistance in the afferent arteriole.…”

Section: Myogenic Responsementioning

confidence: 99%

“…90,91 Some studies have also shown that inhibition of renal T-type channels significantly affects autoregulation. 80,81 However, due to the lack of specific inhibitors of T-type channels results have been difficult to interpret.…”

Section: Renal Autoregulationmentioning

confidence: 99%

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T-type Ca²⁺channels and autoregulation of local blood flow

et al. 2017

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L-type voltage gated Ca2C channels are considered to be the primary source of calcium influx during the myogenic response. However, many vascular beds also express T-type voltage gated Ca 2C channels. Recent studies suggest that these channels may also play a role in autoregulation. At low pressures (40-80 mmHg) T-type channels affect myogenic responses in cerebral and mesenteric vascular beds. T-type channels also seem to be involved in skeletal muscle autoregulation. This review discusses the expression and role of T-type voltage gated Ca 2C channels in the autoregulation of several different vascular beds. Lack of specific pharmacological inhibitors has been a huge challenge in the field. Now the research has been strengthened by genetically modified models such as mice lacking expression of T-type voltage gated Ca 2C channels (Ca V 3.1 and Ca V 3.2). Hopefully, these new tools will help further elucidate the role of voltage gated T-type Ca 2C channels in autoregulation and vascular function.

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No apparent role for T-type Ca2+ channels in renal autoregulation

Frandsen

Salomonsson

Hansen

et al. 2015

Pflugers Arch - Eur J Physiol

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Renal autoregulation protects glomerular capillaries against increases in renal perfusion pressure (RPP). In the mesentery, both L- and T-type calcium channels are involved in autoregulation. L-type calcium channels participate in renal autoregulation, but the role of T-type channels is not fully elucidated due to lack of selective pharmacological inhibitors. The role of T- and L-type calcium channels in the response to acute increases in RPP in T-type channel knockout mice (CaV3.1) and normo- and hypertensive rats was examined. Changes in afferent arteriolar diameter in the kidneys from wild-type and CaV3.1 knockout mice were assessed. Autoregulation of renal blood flow was examined during acute increases in RPP in normo- and hypertensive rats under pharmacological blockade of T- and L-type calcium channels using mibefradil (0.1 μM) and nifedipine (1 μM). In contrast to the results from previous pharmacological studies, genetic deletion of T-type channels CaV3.1 did not affect renal autoregulation. Pharmacological blockade of T-type channels using concentrations of mibefradil which specifically blocks T-type channels also had no effect in wild-type or knockout mice. Blockade of L-type channels significantly attenuated renal autoregulation in both strains. These findings are supported by in vivo studies where blockade of T-type channels had no effect on changes in the renal vascular resistance after acute increases in RPP in normo- and hypertensive rats. These findings show that genetic deletion of T-type channels CaV3.1 or treatment with low concentrations of mibefradil does not affect renal autoregulation. Thus, T-type calcium channels are not involved in renal autoregulation in response to acute increases in RPP.

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Effects of calcium channel blockers on “dynamic” and “steady-state step” renal autoregulation

Abstract: Effects of calcium channel blockers on "dynamic" and "steady-state step" renal autoregulation.

Cited by 47 publications

References 43 publications

Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms

Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms

T-type Ca²⁺channels and autoregulation of local blood flow

No apparent role for T-type Ca2+ channels in renal autoregulation

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Effects of calcium channel blockers on “dynamic” and “steady-state step” renal autoregulation

Abstract: Effects of calcium channel blockers on "dynamic" and "steady-state step" renal autoregulation.

Cited by 47 publications

References 43 publications

Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms

Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms

T-type Ca2+channels and autoregulation of local blood flow

No apparent role for T-type Ca2+ channels in renal autoregulation

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T-type Ca²⁺channels and autoregulation of local blood flow