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Systemic and renal hemodynamic effects of the AT1 receptor antagonist, ZD 7155, and the AT2 receptor antagonist, PD 123319, in conscious lambs

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Abstract

Experiments were carried out to investigate age- and dose-dependent effects of the selective AT1 receptor antagonist, ZD 7155, and the selective AT2 receptor antagonist, PD 123319, on systemic and renal hemodynamics in conscious, chronically instrumented lambs aged ∼1 and ∼6 weeks of postnatal life. Mean arterial pressure (MAP), mean venous pressure (MVP), and renal blood flow (RBF) were measured for 10 min before and for 120 min after ZD 7155, PD 123319, or vehicle. In both age groups, administration of ZD 7155 decreased renal vascular resistance (RVR) and increased RBF within 5 min. These responses lasted less than 90 min but were not dose-dependent. MAP decreased by 30 min after administration of ZD 7155 in both age groups at doses ≥400 μg kg−1; the remaining decreased for up to 120 min, depending upon the dose. Pressor responses to angiotensin II (ANG II) were abolished within 5 min of administration of all doses of ZD 7155, at both 1- and 6 weeks. PD 123319 had no detectable effects on systemic or renal hemodynamics or on the pressor responses to ANG II. Therefore, under physiological conditions in conscious newborn animals, ANG II modulates both resting blood pressure and RVR through activation of AT1 but not AT2 receptors.

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Acknowledgements

This work was supported by an Operating Grant provided by the Canadian Institutes for Health Research and a Grant-in-Aid of Research provided by the Heart and Stroke Foundation of Canada. During the tenure of these experiments, Francine G. Smith was a Heritage Medical Senior Scholar supported by the Alberta Heritage Foundation for Medical Research, and Mona L. Chappellaz was supported by graduate scholarships provided by Alexa W. Church, William Davies, the province of Alberta, and the Department of Medical Science.

A portion of this work was presented in poster format to the annual meetings for Experimental Biology and published in the proceedings (Smith, F.G., Chappellaz, M.L., Systemic and renal haemodynamic responses to the selective AT1 receptor antagonist, ZD 7155, and the selective AT2 receptor antagonist, PD 123319, during postnatal maturation in conscious lambs. FASEB J. 19(4): 2006).

The authors gratefully acknowledge the excellent assistance provided by Miss Karen Connolly and Dr. Wei Qi.

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Correspondence to Francine G. Smith.

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Chappellaz, M.L., Smith, F.G. Systemic and renal hemodynamic effects of the AT1 receptor antagonist, ZD 7155, and the AT2 receptor antagonist, PD 123319, in conscious lambs. Pflugers Arch - Eur J Physiol 453, 477–486 (2007). https://doi.org/10.1007/s00424-006-0148-4

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