Abstract
It was hypothesized that nitric oxide (NO) and prostaglandins (PGs) play a synergistic role in modulating haemodynamic responses to angiotensin II (ANG II) in an age-dependent manner. To this end, experiments were carried out in conscious, chronically instrumented lambs aged ∼1 week (N = 9) and ∼6 weeks (N = 10) to evaluate the haemodynamic responses to ANG II, before and after treatment with the l-arginine analogue, N-nitro-l-arginine methyl ester (l-NAME), as well as the cyclooxygenase inhibitor, indomethacin (INDO). Pressor and renal blood flow responses to ANG II were measured before (control) and after administration of l-NAME (20 mg kg−1), following pretreatment with either vehicle (VEH) (experiment 1) or INDO (1 mg kg−1, experiment 2). The two experiments were carried out at minimum intervals of 48 h. In both age groups, the pressor and renal vasoconstrictor responses to ANG II were augmented by pretreatment with INDO, the effects being similar at 1 and 6 weeks. The haemodynamic responses to ANG II were, however, not altered after l-NAME following pretreatment with either VEH or INDO. These data provide new evidence that soon after birth, endogenously produced PGs, but not endogenously produced NO, balance the vasoconstrictor actions of ANG II. There is, however, no apparent interaction between PGs and NO in modulating the responses to ANG II postnatally.
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Acknowledgements
An operating grant provided by the Canadian Institutes for Health Research supported this work. The authors gratefully acknowledge the expertise of Dr. Wei Qi in surgically instrumenting the experimental animals and carefully critiquing of the manuscript and Ms. Lucy Yu for technical assistance. Dr. Kesavarao K. Ebenezar was supported by a post-doctoral fellowship provided by the Canadian Institutes for Health Research Training Program in Genetics, Child Development, and Health.
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Portion of this manuscript was presented as a poster to Experimental Biology 2008 and published in the proceedings (Ebenezar KK, Wong AKO, Smith FG (2008) Pressor and renal haemodynamic responses to angiotensin II in conscious lambs: role of nitric oxide and prostaglandins. FASEB J 22:735.8).
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Ebenezar, K.K., Wong, A.K.O. & Smith, F.G. Haemodynamic responses to angiotensin II in conscious lambs: role of nitric oxide and prostaglandins. Pflugers Arch - Eur J Physiol 463, 399–404 (2012). https://doi.org/10.1007/s00424-011-1065-8
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DOI: https://doi.org/10.1007/s00424-011-1065-8