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Cardiac beta-adrenoceptors in chronic uremia: studies in humans and rats

Stefan Dhein, MD^*, Peter Röhnert^*, Silke Markau, MD, Emanuel Kotchi-Kotchi, PhD^*, Karin Becker, PhD^*, Ulrike Poller, MD^*, Bernd Osten, MD and Otto-Erich Brodde, PhD^*

^* Institute of Pharmacology and Toxicology, Martin-Luther-University of Halle-Wittenberg, Halle, Germany
Department of Nephrology, Martin-Luther-University of Halle-Wittenberg, Halle, Germany

View larger version (15K): [in a new window]   Figure 1 The effect of intravenous isoprenaline on changes in heart rate (beat/min) in HD patients and healthy volunteers. Values are given as means ± SEM. Significant differences between both groups are indicated by an asterisk (p < 0.05). Basal values: HD patients, 66 ± 4 (n = 4); healthy, 55 ± 3 beats/min (n = 6).

View larger version (15K): [in a new window]   Figure 2 The effect of intravenous isoprenaline on changes in the duration of the heart rate corrected electromechanical systole (QS2c) (ms) in HD patients and healthy volunteers. Values are given as means ± SEM. Significant differences between both groups are indicated by an asterisk (p < 0.05). Basal values: HD patients, 505 ± 16 (n = 4); healthy, 511 ±10 ms (n = 6).

View larger version (12K): [in a new window]   Figure 3 Changes in systolic blood pressure induced by phenylephrine infusion versus changes in heart rate in HD patients (n = 5) and healthy volunteers (n = 6) indicating baroreflex sensitivity. Result of the linear regression is indicated by a solid line for healthy volunteers and by a dashed line for HD patients. Data of linear regression are given in the text.

View larger version (15K): [in a new window]   Figure 4 The effect of intravenous injection of pirenzepine (0.16, 0.32, 0.64 and 1.25 mg, 20 min per dose step) on heart rate in healthy volunteers (n = 6) and HD patients (n = 5). Values are given as means ± SEM.. There were no significant differences between both groups. Baseline heart rate: healthy, 57 ± 2; HD patients, 70 ± 3 beats/min; p < 0.05).

View larger version (22K): [in a new window]   Figure 5 (A) Changes in the contractile responses of isolated left ventricular strips of uremic (SNX) and sham-operated (SOP) rats to cumulative concentrations of isoprenaline. Control values: SNX, 4.5 ± 0.27 (n = 15); SOP, 3.5 ± 0.24 mN (n = 9). (B) Changes in the calcium-induced positive inotropic response in SOP and SNX rats. Control values: SNX, 2.3 ± 0.3 mN (n = 15); SOP, 1.67 ± 0.2 mN (n = 9). (C) Decrease in contractile force in ventricular strips prestimulated with 3 µmol/liter forskolin by cumulative concentrations of carbachol in SOP (n = 3) and SNX (n = 3) rats. Control values after preconstriction with 3 µmol/liter forskolin: SNX, 5.7 ± 0.4 mN (n = 3); SOP, 6.5 ± 0.7 mN (n = 3). All values are given as means ± SEM. Significant differences between both groups are indicated by an asterisk (* = p < 0.05; ** = p < 0.01; *** = p < 0.001).

View larger version (17K): [in a new window]   Figure 6 Changes in adenylyl cyclase activity in sham-operated (SOP) (n = 9) and uremic (SNX) rats (n = 7) after stimulation with isoprenaline given as means ± SEM. For details of the protocol, see text. Significant differences between both groups are indicated by an asterisk (pD2 values: SOP, 8.18 ± 0.25; SNX, 7.95 ± 0.24, NS).