Cyclosporine A modulates baroreceptor function in kidney transplant recipients

Gerhardt, Ulf; Riedasch, M.; Hohage, Helge

doi:10.1016/s0167-5273(98)00368-4

Cited by 22 publications

(17 citation statements)

References 25 publications

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“…Cyclosporine A, one of the most effective immunosuppressant agents, has been shown in clinical and experimental studies to impair the arterial baroreceptor function (Ryuzaki et al, 1997;Gerhardt et al, 1999;Lucini et al, 2000). The cyclosporine-induced baroreflex dysfunction has been implicated in the pressor effect that develops during cyclosporine therapy (Gerhardt et al, 1999;Lucini et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Attenuation of arterial baroreceptor responsiveness is another mechanism that may contribute to cyclosporine-induced hypertension. Gerhardt et al (1999) have shown that cyclosporine elevates blood pressure in kidney transplant recipients, and this effect was associated with a reduced baroreflex function. Cyclosporine has also been shown to shift the midranges of baroreflex control of sympathetic nerve activity and heart rate to higher arterial pressures (Ryuzaki et al, 1997).…”

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confidence: 99%

“…It has been suggested that an imbalance between the sympathetic and parasympathetic activities due to an enhanced sympathetic tone may explain cyclosporine-induced baroreflex dysfunction (Gerhardt et al, 1999). Cyclosporine increases the production of thromboxane A 2 and disturbs the prostaglandin (prostaglandin I 2 and thromboxane A 2 ) balance (Perico et al, 1986).…”

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confidence: 99%

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Cyclosporine Adversely Affects Baroreflexes via Inhibition of Testosterone Modulation of Cardiac Vagal Control

El‐Mas

Afify²,

Omar³

et al. 2002

The Journal of Pharmacology and Experimental Therapeutics

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Previous studies have shown that the immunosuppressant drug cyclosporine A attenuates arterial baroreceptor function. This study investigated whether the modulatory effect of cyclosporine on baroreceptor function involves inhibition of the baroreflex-facilitatory effect of testosterone. The role of cardiac autonomic control in cyclosporine-testosterone baroreflex interaction was also investigated. Baroreflex curves relating bradycardic responses to increments in blood pressure evoked by phenylephrine were constructed in conscious, sham-operated, castrated rats and in testosterone-replaced castrated (CAS ϩ T) rats in the absence and presence of cyclosporine. The slopes of the curves were taken as an index of the baroreflex sensitivity (BRS). Short-term (11-13 days) cyclosporine treatment or castration reduced plasma testosterone levels and caused similar attenuation of the reflex bradycardia, as indicated by the significantly smaller BRS compared with sham-operated values (Ϫ0.97 Ϯ 0.07, Ϫ0.86 Ϯ 0.06, and Ϫ1.47 Ϯ 0.10 beats/min/mm Hg, respectively). The notion that androgens facilitate baroreflexes is further confirmed by the observation that testosterone replacement of castrated rats restored plasma testosterone and BRS to sham-operated levels. Cyclosporine had no effect on BRS in castrated rats but caused a significant reduction in CAS ϩ T rats. Muscarinic blockade by atropine caused approximately 60% reduction in the BRS in sham-operated rats, an effect that was significantly and similarly diminished by castration, cyclosporine, or their combination. ␤-Adrenergic blockade by propranolol caused no significant changes in BRS. These findings suggest that cyclosporine attenuates baroreflex responsiveness via, at least partly, inhibition of the testosteroneinduced facilitation of cardiomotor vagal control.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Cyclosporine Adversely Affects Baroreflexes via Inhibition of Testosterone Modulation of Cardiac Vagal Control

El‐Mas

Afify²,

Omar³

et al. 2002

The Journal of Pharmacology and Experimental Therapeutics

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“…This observation may be spurious, since the numbers were small. Nevertheless, cyclosporine has been shown to increase sympathetic-nerve activity 31 and to decrease brachialartery distensibility. 32 Since an increased resistance index was correlated most closely with the pulse pressure, a crude marker of vascular stiffness, a substance such as moxonidine that inhibits sympathetic-nerve activity could positively influence vascular stiffness in renal-transplant recipients.…”

Section: Correlations With Other Measuresmentioning

confidence: 99%

The Renal Arterial Resistance Index and Renal Allograft Survival

et al. 2003

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“…Nonetheless, whether the attenuation of BRS contributes to the acute pressor effect of CsA has not been investigated. Notably, CsA-induced inhibition of BRS has been implicated in the chronic pressor effect of the drug (Gerhardt et al, 1999;Lucini et al, 2000). Other proposed mechanisms include 1) endothelial dysfunction (Oriji and Keiser, 1999) and direct vasoconstriction (Xue et al, 1987;Lo Russo et al, 1997), 2) induction of endothelin release (Grieff et al, 1993), 3) inhibition of endothelin inactivating peptidase (Janas et al, 1994), and 4) activation of afferent nerve firing from subdiaphragmatic region with a reflex sympathetic activation, which was shown to be related to calcineurin enzyme inhibition (Moss et al, 1985;.…”

mentioning

confidence: 99%

Cyclosporine Induces Progressive Attenuation of Baroreceptor Heart Rate Response and Cumulative Pressor Response in Conscious Unrestrained Rats

Shaltout¹,

Abdel‐Rahman²

2003

The Journal of Pharmacology and Experimental Therapeutics

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Cyclosporine A (CsA) use is associated with hypertension and reduced baroreceptor sensitivity (BRS), but the underlying mechanisms remain unresolved. In this study, we investigated whether CsA attenuation of BRS is 1) dependent on treatment regimen, and 2) causative of the pressor response. Furthermore, we investigated whether a reduction in plasma testosterone contributes to BRS attenuation caused by short-term CsA administration. The effects of the clinically used CsA formulation (15 mg/kg/day i.v. for 5 days) on mean arterial pressure (MAP), heart rate, BRS, and body weight were investigated in conscious rats. CsA caused reproducible pressor responses (15.1 Ϯ 3.0 mm Hg) starting after the first dose and continuing through the 5 days of the study. BRS and baseline MAP were inversely related in the CsA group because of a progressive reduction in BRS, which started on day 2 and reached ϳ50% of baseline on day 5 and a cumulative elevation in MAP. The inverse BRS and MAP responses required daily administration of CsA because neither response was evident throughout the 5-day observation period after a single dose of CsA. Plasma testosterone levels were similar in all groups, whereas the body weight decreased approximately 10% in the CsA group on day 5. These findings suggest 1) CsA attenuation of BRS is relatively rapid and cumulative; 2) the attenuation of BRS may contribute to the delayed, but not to the acute, pressor elicited by CsA; and 3) the cumulative reduction in BRS caused by short-term (5-day) CsA treatment is not testosterone-related.

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Cyclosporine A modulates baroreceptor function in kidney transplant recipients

Cited by 22 publications

References 25 publications

Cyclosporine Adversely Affects Baroreflexes via Inhibition of Testosterone Modulation of Cardiac Vagal Control

Cyclosporine Adversely Affects Baroreflexes via Inhibition of Testosterone Modulation of Cardiac Vagal Control

The Renal Arterial Resistance Index and Renal Allograft Survival

Cyclosporine Induces Progressive Attenuation of Baroreceptor Heart Rate Response and Cumulative Pressor Response in Conscious Unrestrained Rats

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