Brooks, David Patrick (1979) Angiotensin II in the rat. University of Southampton, Doctoral Thesis.
Abstract
Angiotensln II Is an Important hormone Involved in the regulation of the body's salt and water balance. This thesis describes work on the rate of angiotensin II breakdown in the rat in vivo and on the renal actions of angiotensin 11.An original method is described for estimating the rate at which the hormone angiotensin II is removed from the circulatory system. The method Involves studying the time course of the biological response evoked by this hormone. Five criteria were identified and satisfied to Indicate that this method gives reliable results, and It is suggested that these results are more accurate than most previous estimates.The half-life of angiotensin II in the circulating system was found to be 16 t 1 seconds. Some structural changes to the angiotensin molecule (e.g. removal of the aspl residue or replacement with asn) had no effect on the half-life of the hormone, but substitution of the. aspt residue with sarcosine greatly prolonged the half-life, which may account for the known potency of this molecule. The half-life of angiotensin Itamide was Increased by pentobarbitone anaesthesia and by hypothermia (cooling to 250C); however, long term dietary sodium changes had no effect on the half-life of the hormone. This is an Important observation showing that changes to angiotensin 11 breakdown rate are not involved to the normal control of salt balance.The actions of angiotensin 11 on renal function were studied and itwas observed that: (1) angiotensin It causes reductions in urinary salt and water excretion, primarily by virtue of its actions on the renal blood vessels; (2) these actions of angiotensin II are, at least in part, dependent on the production of prostaglandins within the kidney; (3) the biphasic response of the kidney to a high dose of angiotensin It is caused by the Interaction between two different components of the renal response, viz. a natriuretic and an antinatriuretic component. Experimental evidence is presented which suggests that both componentsare present throughout the Infusion of angiotensin II, and that the antinatriuretic response is dominant for the first five minutes but then tachyphylaxis occurs, allowing the natriuretic component to become dominant.
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