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Updated: Jul 24, 2026

Two-photon Imaging of Intracellular Ca2+ Handling and Nitric Oxide Production in Endothelial and Smooth Muscle Cells of an Isolated Rat Aorta
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Nitric oxide in CsA-induced hypertension: role of beta-adrenoceptor antagonist and thromboxane A2

G K Oriji1, N Schanz

  • 1Hypertension-Endocrine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Orijig@wpunj.edu

Prostaglandins, Leukotrienes, and Essential Fatty Acids
|May 8, 2002
PubMed

Insights

Cyclosporine A (CsA) causes hypertension by reducing nitric oxide (NO) and increasing thromboxane A2 (TBXA2) and protein kinase C (PKC) activity. Propranolol reversed these effects, suggesting a role for beta-adrenoceptors in CsA-induced hypertension.

Area of Science:

  • Pharmacology
  • Cardiovascular Physiology
  • Immunology

Background:

  • Cyclosporine A (CsA) is a widely used immunosuppressant.
  • CsA is known to induce hypertension, but the underlying mechanisms are not fully understood.
  • Vascular responses and endothelial function are implicated in CsA-induced hypertension.

Purpose of the Study:

  • To investigate the effects of CsA on vascular responses in rats.
  • To determine the impact of CsA on nitric oxide (NO) and thromboxane A2 (TBXA2) production.
  • To explore the role of protein kinase C (PKC) and beta-adrenoceptors in CsA-mediated hypertension.

Main Methods:

  • CsA was administered to Sprague-Dawley rats for 7 days.
  • Mean arterial pressure (MAP), urinary nitrate/nitrite (NO2/NO3), and thromboxane A2 (TBXA2) levels were measured.
  • Vascular responses were assessed in isolated rat aortic rings, and protein kinase C (PKC) activation was evaluated.

Main Results:

  • CsA administration significantly increased MAP and TBXA2 production while decreasing NO2/NO3 levels.
  • In vitro, CsA reduced NO2/NO3 production and increased TBXA2 production in aortic rings.
  • CsA activated PKC translocation in rat aorta, and propranolol reversed the hypertensive effects of CsA both in vivo and in vitro.

Conclusions:

  • CsA induces hypertension by inhibiting endothelial NO formation, activating PKC, and increasing TBXA2 production.
  • Beta-adrenoceptor antagonism with propranolol effectively counteracts CsA-induced hypertension.
  • These findings suggest that CsA-mediated hypertension involves complex vascular alterations that can be modulated by beta-blockers.

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