Ciclosporin A inhibits endothelium-dependent vasodilatation and vascular prostacyclin production

Bossaller, Claus; Förstermann, Ulrich; Hertel, Rolf F.; Olbricht, Christoph J.; Reschke, Volkmar; Fleck, Eckart

doi:10.1016/0014-2999(89)90785-1

Cited by 86 publications

(36 citation statements)

References 8 publications

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“…7 " In the rat this effect is not a consequence of increased blood pressure, since CsA does not significantly increase blood pressure in normotensive rats. 10 -12 We chose this model to determine possible protective effects of chronic ACE inhibition on endothelial function, since CsA has been shown to augment selectively the effects of Ang II in rat vascular smooth muscle.…”

Section: Hronic Angiotensin-converting Enzyme (Ace)mentioning

confidence: 98%

Vasomotor responses in cyclosporin A-treated rats after chronic angiotensin blockade.

Auch-Schwelk¹,

Duske²,

Hink³

et al. 1994

Hypertension

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Chronic angiotensin-converting enzyme (ACE) inhibition prevents endothelial dysfunction in hypertension and hypercholesterolemia. Long-term treatment with cyclosporin A impairs endothelium-dependent relaxations and augments contractions to angiotensin II in the rat aorta. The present study compares vasomotor responses to several vasoconstrictor and dilator stimuli after 6 weeks of oral treatment with either the angiotensin-converting enzyme inhibitor lisinopril (10 mg/kg per day), the angiotensin subtype 1 receptor antagonist D 8731 (10 mg/kg per day), cyclosporin A (15 mg/kg per day), or a combination of cyclosporin A with lisinopril or D 8731 (n=15 rats per group). Twenty-four hours after the last treatment, aortic rings were mounted in organ chambers for measurement of isometric force. Endotheliumdependent relaxations to acetylcholine and calcium ionophore were impaired by cyclosporin A but not affected by the vasodilators. Cyclosporin A-induced endothelial dysfunction was prevented by cotreatment with lisinopril or D 8731. C hronic angiotensin-converting enzyme (ACE)inhibition prevents endothelial dysfunction in animal models with hypertension and hypercholesterolemia. 13 Even in hypertensive animals the modulation of endothelial function is not exclusively explained by the reduction of blood pressure, since treatment with hydralazine does not modify endothelium-dependent relaxations to the same extent, if at all. 1Considering additional studies showing reduced intima formation after endothelial injury and reduced development of atherosclerosis during ACE inhibition, 46 it has been hypothesized that chronic ACE inhibition protects or restores endothelial function. Both reduced angiotensin II (Ang II) formation and bradykinin accumulation during ACE inhibition have been discussed as mechanisms contributing to these effects.Long-term treatment with cyclosporin A (CsA) impairs endothelium-dependent relaxations in rats and humans.7 " In the rat this effect is not a consequence of increased blood pressure, since CsA does not significantly increase blood pressure in normotensive rats. 10 -12 We chose this model to determine possible protective effects of chronic ACE inhibition on endothelial function, since CsA has been shown to augment selectively the effects of Ang II in rat vascular smooth muscle. cidate the contribution of Ang II to these effects. In addition, we assessed the modulation of vascular smooth muscle contractions to Ang II and other vasoconstrictors by these treatments. CsA dosage was reduced compared with previous studies to reduce toxic side effects and to reach blood concentrations close to the therapeutic range.7 ' 10

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Section: Hronic Angiotensin-converting Enzyme (Ace)mentioning

confidence: 98%

Vasomotor responses in cyclosporin A-treated rats after chronic angiotensin blockade.

Auch-Schwelk¹,

Duske²,

Hink³

et al. 1994

Hypertension

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“…73,74 Marumo and colleagues 75 however also showed that cyclosporin A inhibited inducible nitric oxide synthase activity in rat aortic smooth muscle cells. Administration of larginine to spontaneously hypertensive rats protects against the pressor effects of cyclosporin.…”

Section: Cyclosporin and Vasodilator Activitymentioning

confidence: 99%

“…Administration of larginine to spontaneously hypertensive rats protects against the pressor effects of cyclosporin. 73,74 Cyclosporin and the sympathetic nervous system: There is controversy about effects of cyclosporin on the sympathetic nervous system. This may partly arise from species differences in responses to cyclosporin treatment.…”

Section: Cyclosporin and Vasodilator Activitymentioning

confidence: 99%

Hypertension in thoracic transplant recipients

Jenkins

Singer

1998

J Hum Hypertens

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There are many mechanisms underlying the hypertension which occurs after thoracic transplantation. Previous disease, effects of cyclosporin, tacrolimus and steroid immunosuppression and cardiac denervation are major contributory factors. Abnormal sodium and water balance is an important common mediating factor. A new approach is clearly needed for classifying the severity of hypertension in these patients taking into account day-night variation and total blood pressure

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“…It has been shown that in a number of different vascular beds and isolated blood vessels, cyclosporin can cause reductions in the degree of endothelium-dependent relaxation. [63][64][65][66][67] In addition, in vivo studies using two-dimensional and Doppler ultrasound showed that acute administration of cyclosporin impaired the dilator effect of acetylcholine. 63 This effect was independent of the vehicle used to dissolve the drug, or an increase in circulating levels of endothelin.…”

Section: Cyclosporin-induced Endothelial Toxicitymentioning

confidence: 99%