Faculty Collaboration Database

Role of endogenous ANG II and AT1 receptors in regulating arterial baroreflex responses in newborn lambs. Am J Physiol 1997 Jun;272(6 Pt 2):R1862-73

Date

06/01/1997

Pubmed ID

9227601

DOI

10.1152/ajpregu.1997.272.6.R1862

Scopus ID

2-s2.0-0030787054   23 Citations

Abstract

The present study was designed to test the hypothesis that endogenous angiotensin II (ANG II) influences baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) early in life and to determine whether these actions are mediated by angiotensin AT1 or AT2 receptors. To test this hypothesis, we studied the effects of systemic and central administration of losartan, a selective AT1 receptor antagonist, and PD-123319, a selective AT2 antagonist, on baroreflex-mediated control of HR and RSNA in conscious newborn lambs. Systemic administration of losartan decreased resting mean arterial blood pressure (MABP) from 70 +/- 3 to 58 +/- 4 mmHg (P < 0.05) without producing reflex increases in HR or RSNA. The baroreflex response curves were shifted to the left as indicated by a decrease in the arterial pressure at the midpoint of the curve for HR (83 +/- 3 to 75 +/- 4 mmHg) and RSNA (74 +/- 2 to 69 +/- 3 mmHg; P < 0.05 for both). Losartan also reset HR and RSNA baroreflex curves when changes in baseline blood pressure were prevented by simultaneous infusion of phenylephrine. In contrast, a sustained decrease in arterial pressure of 10-12 mmHg with nitroprusside failed to shift the baroreflex function curves. PD-123319 had no effect on baseline HR, MABP, RSNA, or baroreflex responses. Lateral ventricle administration of losartan but not PD-123319 also produced a decrease in arterial pressure (81 +/- 4 to 73 +/- 3 mmHg, P < 0.05) and reset the baroreflex for HR and RSNA toward lower pressure. These results demonstrate that, early in life, endogenous ANG II exerts a tonic effect on baroreflex control of HR and RSNA to shift the curves toward higher pressure levels. The alterations in arterial baroreflex function appear independent of direct ANG II effects on arterial pressure and are mediated by AT1 receptors.

Author List

Segar JL, Minnick A, Nuyt AM, Robillard JE

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Animals, Newborn
Antihypertensive Agents
Arteries
Baroreflex
Biphenyl Compounds
Cardiovascular Physiological Phenomena
Imidazoles
Losartan
Phenylephrine
Receptors, Angiotensin
Sheep
Tetrazoles