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Title: The role of angiotensin in the control of blood pressure : a functional interaction with the autonomic nervous system
Author: Hatton, R.
Awarding Body: CNAA
Current Institution: Open University
Date of Award: 1987
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An interaction of the renin-angiotensin system and the autonomic nervous system was demonstrated in vivo during activation of the former by sodium depletion in the dog and the latter during application of lower body negative pressure (LBNP) in the cat. In the dog, inhibitors of angiotensin converting enzyme (ACE), teprotide and captopril, together with an angiotensin II (AII) antagonist, saralasin, and a peptide inhibitor of renin, H77, given intravenously lowered blood pressure (BP) by reducing peripheral resistance in relation to the prevailing level of plasma renin activity (PRA). They did so without changing cardiac output or heart rate as PRA rose above the resting level. The lack of tachycardia was due to a resetting of the baroreflex without a change in sensitivity as teprotide unmasked an action of AII at a peripheral site since when administered into a lateral cerebral ventricle it was ineffective. In the cat, teprotide and saralasin enhanced the fall in BP induced by LBNP and impaired its recovery. When these inhibitors were given during LBNP, a greater and more sustained fall in BP was seen than with either inhibitor alone. This occurred before activation of plasma renin and was not associated with a reduction in sympathetic efferent nerve activity. Further studies revealed that teprotide, captopril and enalapril interfered with neurogenic vasoconstriction involving AII in pithed rats and moreover, captopril was active in lowering BP in two strains of rat shown to be particularly sensitive to the adrenergic potentiating effect of AII. These findings have provided physiological evidence in vivo supporting a peripheral interaction between the autonomic nervous system and AII even at low levels of activation which potentiate adrenergic mechanisms and maintain homeostatic reflexes. They suggest that a significant part of the hypotensive activity of ACE inhibitors is due to interference with facilitatory actions of AII on the autonomic nervous system.
Supervisor: Not available Sponsor: Imperial Chemical Industries plc
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Drug control of hypertension