Determination Of Turnover Rates Research Articles

Abstract P174: Dynamics of the Renin-Angiotensin-Aldosterone System: Implications of Angiotensin-Peptide Fingerprinting on the Clinical Use and Development of Antihypertensive Drugs

BACKGROUND: The Renin-Angiotensin-Aldosterone-System (RAAS) is an extensively studied peptide hormone system which is critically involved in the regulation of blood pressure and other important physiologic functions. Angiotensin-(1-10) which is liberated from angiotensinogen by kidney secreted Renin, is sequentially metabolized to different N- and C-terminal truncated fragments with partially described biologic activities. Beside Angiotensin II (Ang-(1-8)), various other angiotensin peptides including Ang-(1-7), Ang-(1-9), Ang-(2-8) and Ang-(3-8) are known to possess physiologic activity while Ang-(1-7) and more recently Ang-(1-9) were described to antagonize pathologic effects of Ang-(1-8) via vasodilation and antifibrotic action respectively. The role of Ang-(1-8) in hypertension converts enzymes participating in Ang-(1-8) generation to favorable targets for antihypertensive drugs. METHODS: Human blood was collected from healthy volunteers followed by ex-vivo incubation at 37°C in the presence of different inhibitors of angiotensin metabolism. Angiotensin concentrations were determined employing a novel sensitive LC-MS/MS based method, which allows the simultaneous quantification of a broad panel of angiotensin peptides in human plasma. RESULTS: The investigation of different angiotensin metabolism modifiers revealed agent specific patterns of angiotensin peptide levels reflecting the specificity of these inhibitors. Spiking experiments allowed the determination of turnover rates for distinct angiotensin conversion reactions surrounded by their physiological matrix. CONCLUSION: The measurement of blood concentrations of angiotensin peptides provides important information about the substrate specificities and activities of enzymes involved in their metabolism. This allows the identification of potential causes for pathologic conditions, facilitating a patient specific therapeutic modulation of the RAAS. The overall assessment of angiotensin peptide concentrations (Angiotensin-Peptide-Fingerprinting) represents a powerful tool to gain a more detailed understanding of blood pressure regulation, enabling the pharmacologic characterization of RAAS modifying agents in use and development.

Measurement of specific radioactivity by high-performance liquid chromatograph with a synchronized accumulating radioisotope detector: Determination of turnover rate and pool size of tryptophan in rat

A high-performance liquid chromatograph with a synchronized accumulating radioisotope detector was used to determine the turnover rate and pool size of tryptophan in rat. The specific radioactivity could be followed for three half-lives on the final slope of the specific radioactivity curve following intravenous administration of 15 μCi of carrier free tryptophan labeled with carbon-14. Remarkable individual differences were noted in turnover rate and in pool size among rats.

The application of island-biogeographic theory to forest tracts: Problems in the determination of turnover rates

Abstract Any change in the species-composition of birds on ‘islands’ may be described potentially by a number of models, one of which is the equilibrium island biogeographic model. The proper application of the equilibrium model requires that several conditions be met; the most important of which are: (1) the ability to identify true ‘colonists’; (2) balanced immigration and extinction rates; and (3) no large-scale environmental alterations causing changes in species-composition between sampling intervals. Failure to meet such conditions may lead to improbable or unrealistic interpretations of species change within the context of equilibrium island biogeographic theory. This problem is illustrated with some recent data on birds residing in a small forest patch. When the theory is used to determine the design characteristics of faunal reserves, the entire matter takes on added significance. Ecological justification for the preservation of large, contiguous areas cannot be gained from the equilibrium model. In addition, predictions of the model are virtually useless without an accompanying body of autecological information on the species intended to be preserved.

Biosynthetic determination of turn-over rates of various plasma proteins in normal and cirrhotic man

Biosynthetic determination of turn-over rates of various plasma proteins in normal and cirrhotic man