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On The Mechanism Of The Cyclosporine‐Evoked Facilitation Of The Vasoconstrictor Activity Of Angiotensin II In The Rat Aorta
Author(s) -
Nasser Suzanne A,
Elmallah Ahmed I,
Sabra Ramzi,
Khedr Mohamed M,
ElDin Mahmoud M Mohy,
ElMas Mahmoud M
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb593
Subject(s) - losartan , angiotensin ii , angiotensin ii receptor type 1 , endothelin receptor , cyclooxygenase , chemistry , nitric oxide , pharmacology , nitric oxide synthase , endocrinology , receptor , medicine , thromboxane a2 , captopril , thromboxane , enzyme , blood pressure , platelet , biochemistry
Despite the established role of enhanced vasoconstrictor responsiveness to angiotensin II (Ang II) in the hypertensive action of the immunosuppressant drug cyclosporine (CSA), the precise mechanism remains unclear. In this contribution, pharmacological studies were undertaken to investigate the potential involvement of vasomotor pathways in the CSA‐Ang II vascular interaction. The chronic treatment of rats with CSA (25 mg/kg/day i.p., 7 days) increased the aortic contractile responses elicited by Ang II (1×10 −10 –3×10 −7 M), with increases and decreases in E max and EC 50 , respectively. The concurrent blockade of angiotensin AT1 receptors (losartan), or the inhibition of angiotensin converting enzyme (captopril), cyclooxygenase (indomethacin) or nitric oxide synthase (L‐NAME) abolished the CSA‐evoked augmentation in Ang II contractions. The combined, but not individual, treatment with endothelin ETA (atrasentan) and ETB (BQ788) receptors also abolished the CSA effect. The enhancement of Ang II contractions by CSA was preserved after selective blockade of thromboxane A2 receptors by terutroban. Together, these findings reveal a positive modulatory role for endothelin receptors and products of cyclooxygenase and nitric oxide synthase activity in the CSA‐Ang II vascular interaction.