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Rho‐kinase inhibition abolishes the vasoconstrictor response to hypoxia in the infant piglet pulmonary arterial circulation
Author(s) -
Balasundaram Naveen,
Chowdhary Paraag,
Titus James,
Jagannath Anand,
Carillo Kathleen,
Myers Jeff L
Publication year - 2009
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.23.1_supplement.lb50
Subject(s) - fasudil , hypoxic pulmonary vasoconstriction , hypoxia (environmental) , vasoconstriction , medicine , rho associated protein kinase , blood pressure , pulmonary hypertension , pulmonary artery , cardiology , anesthesia , kinase , chemistry , oxygen , biochemistry , organic chemistry
We examined the effects of the rho‐kinase inhibitor fasudil on the regional response of the infant pulmonary arterial (PA) circulation to hypoxia. 15 two week old piglets were instrumented to record PA pressure (PAP). Control animals (n=7) were exposed to hypoxia (FiO 2 = 0.05). Treated animals (n=8) were infused with fasudil (5mg/Kg) before and during hypoxia. Input mean impedance (Zm, reflecting distal arteriolar vasoconstriction) and characteristic impedance (Zo, reflecting proximal arteriolar opposition to flow) were calculated. Hypoxia caused a potent vasoconstrictor response distally (increased Zm). Zo was unchanged indicating no alteration of the proximal circulation. Pre‐treatment with fasudil completely abolished the increase in Zm and PAP indicating that the distal vasoconstrictor response is rho‐kinase dependent. Rho‐kinase inhibitors may be an effective therapy for hypoxic pulmonary hypertension in infants, but may be limited by its effect on systemic blood pressure. Funded by Dept. of Surgery, Mass. Gen. Hosp.