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

2004 ◽  
Vol 286 (6) ◽  
pp. F1136-F1143 ◽  
Author(s):  
Karen A. Griffin ◽  
Rifat Hacioglu ◽  
Isam Abu-Amarah ◽  
Rodger Loutzenhiser ◽  
Geoffrey A. Williamson ◽  
...  
Keyword(s):  
Steady State ◽  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Beat Frequency ◽  
Resonance Peak ◽  
Tubuloglomerular Feedback ◽  
Channel Blockers ◽  
Control Mechanisms ◽  
Sprague Dawley ◽  
Renal Autoregulation

Renal autoregulation (AR) mechanisms provide the primary protection against transmission of systemic pressures and hypertensive renal damage. However, the relative merits of the “step” change vs. “dynamic” methods for the assessment of AR capacity remain controversial. The effects of 48–72 h of orally administered amlodipine (L-type) and mibefradil (T-type) calcium channel blockers (CCBs) on step and dynamic AR in Sprague-Dawley rats were compared. Both CCBs significantly impaired “steady-state step” AR (autoregulatory indexes = ∼0.5 vs. ∼0.1 in controls, P < 0.05; n = 9–10/group). By contrast, dynamic AR compensation in separate conscious rats ( n = 12) was not significantly altered by either amlodipine ( n = 10) or mibefradil ( n = 6; fractional gain in admittance ∼0.4–0.5 in all groups at frequencies in the range of 0.0025–0.025 Hz). However, both CCBs tended to attenuate the myogenic resonance peak along with shifting it to a significantly slower frequency ( P < 0.001) during dynamic AR, but no consistent effects were observed on the tubuloglomerular feedback resonance peak. While the reasons for the insensitivity of dynamic vs. steady-state step AR capacity estimates to CCBs remain to be established, the present data indicate that dynamic AR methods may have a limited utility for assessing AR capacity but may provide potentially important insights into the operational characteristics of AR control mechanisms. A strong correlation was also observed between the average conductance and the admittance gain at the heart beat frequency ( r = 0.77, P < 0.001), suggesting that such parameters may provide additional and possibly more meaningful indexes of BP transmission in conscious animals during dynamic AR.

Changes of action potential and L-type calcium channel current of Sprague–Dawley rat ventricular myocytes by different amlodipine isomers

2008 ◽  
Vol 86 (9) ◽  
pp. 620-625 ◽  
Author(s):  
Ru-xing Wang ◽  
Wen-ping Jiang
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Calcium Channel ◽  
Ventricular Myocytes ◽  
Channel Blockers ◽  
Sprague Dawley ◽  
Patch Clamp Technique ◽  
Rat Ventricular Myocytes ◽  
Channel Current ◽  
Steady State Inactivation

To investigate the effects of S- and R-amlodipine (Aml) on action potential (AP) and L-type calcium channel current (ICa-L), the whole-cell patch-clamp technique was used on rat ventricular myocytes to record AP, ICa-L, peak currents, steady-state activation currents, steady-state inactivation currents, and recovery currents from inactivation with S-Aml and R-Aml at various concentrations. Increasing concentrations of S-Aml gradually shortened AP durations (APDs). At concentrations of 0.1, 0.5, 1, 5, and 10 μmol/L, S-Aml blocked 1.5% ± 0.2%, 25.4% ± 5.3%, 65.2% ± 7.3%, 78.4% ± 8.1%, and 94.2% ± 5.0% of ICa-L, respectively (p < 0.05), and the half-inhibited concentration was 0.62 ± 0.12 µmol/L. Current–voltage curves were shifted upward; steady-state activation and inactivation curves were shifted to the left. At these concentrations of S-Aml, the half-activation voltages were –16.01 ± 1.65, –17.61 ± 1.60, –20.17 ± 1.46, –21.87 ± 1.69, and –24.09 ± 1.87 mV, respectively, and the slope factors were increased (p < 0.05). The half-inactivation voltages were –27.16 ± 4.48, –28.69 ± 4.52, –31.19 ± 4.17, –32.63 ± 4.34, and –35.16 ± 4.46 mV, respectively, and the slope factors were increased (p < 0.05). The recovery times from inactivation of S-Aml were prolonged (p < 0.05). In contrast, R-Aml had no effect on AP and ICa-L (p > 0.05) at the concentrations tested. Thus, only S-Aml has calcium channel blockade activity, whereas R-Aml has none of the pharmacologic actions associated with calcium channel blockers.

Tubuloglomerular feedback responses during peritubular infusions of calcium channel blockers

1990 ◽  
Vol 258 (3) ◽  
pp. F537-F544 ◽  
Author(s):  
K. D. Mitchell ◽  
L. G. Navar
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Calcium Flux ◽  
Channel Blockers ◽  
Peritubular Capillary ◽  
Arterial Blood ◽  
Feedback Responses

Experiments were performed in pentobarbital-anesthetized rats to evaluate the dependence of the effector limb of the tubuloglomerular feedback mechanism on transmembrane calcium flux through potential-operated calcium channels. Peritubular capillary infusions of the calcium channel blockers, verapamil and nifedipine, were used to achieve high intrarenal levels without influencing arterial blood pressure. Proximal tubule stop-flow pressure (SFP) and single-nephron glomerular filtration rate (SNGFR) tubuloglomerular feedback responses were obtained during control conditions and during simultaneous peritubular capillary infusion with an isotonic saline solution containing either verapamil or nifedipine. Infusion of either 10(-3) M verapamil or 10(-3) M nifedipine, at a rate of 20 nl/min, increased resting SFP (measured during conditions of zero distal volume delivery) and markedly attenuated both the SFP and SNGFR feedback responses to a late proximal perfusion rate of 30 nl/min. Infusion of verapamil (10(-3) M) also increased the slope of the relationship between SFP and renal arterial perfusion pressure between 80 and 120 mmHg (0.43 +/- 0.03 vs 0.24 +/- 0.02, P less than 0.001, n = 10). These findings support the hypothesis that the preglomerular contractile elements responsive to signals from the macula densa cells are activated by calcium influx through potential-operated calcium channels. Furthermore, the preglomerular contractile elements sensitive to calcium channel blockers can dilate further even when orthograde flow to a single macula densa segment is interrupted.

Electroanalytical Methods for Determination of Calcium Channel Blockers

2019 ◽  
Vol 15 (3) ◽  
pp. 207-218 ◽  
Author(s):  
Fatma Ağın
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Channel Blocker ◽  
Heart Diseases ◽  
Dosage Forms ◽  
Channel Blockers ◽  
Electroanalytical Methods ◽  
Pharmaceutical Dosage Forms ◽  
Ischemic Heart Diseases

Background:Calcium Channel Blockers (CCBs) are widely used in the treatment of cardiovascular and ischemic heart diseases in recent years. They treat arrhythmias by reducing cardiac cycle contraction and also benefit ischemic heart diseases. Electroanalytical methods are very powerful analytical methods used in the pharmaceutical industry because of the determination of therapeutic agents and/or their metabolites in clinical samples at extremely low concentrations (10-50 ng/ml). The purpose of this review is to gather electroanalytical methods used for the determination of calcium channel blocker drugs in pharmaceutical dosage forms and biological media selected mainly from current articles.Methods:This review mainly includes recent determination studies of calcium channel blockers by electroanalytical methods from pharmaceutical dosage forms and biological samples. The studies of calcium channel blockers electroanalytical determination in the literature were reviewed and interpreted.Results:There are a lot of studies on amlodipine and nifedipine, but the number of studies on benidipine, cilnidipine, felodipine, isradipine, lercanidipine, lacidipine, levamlodipine, manidipine, nicardipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, diltiazem, and verapamil are limited in the literature. In these studies, DPV and SWV are the most used methods. The other methods were used less for the determination of calcium channel blocker drugs.Conclusion:Electroanalytical methods especially voltammetric methods supply reproducible and reliable results for the analysis of the analyte. These methods are simple, more sensitive, rapid and inexpensive compared to the usually used spectroscopic and chromatographic methods.

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