('125)I-tonin injected intravenously to rats dissappeared from plasma with a bi-exponential decline. The label accumulated in the liver, adrenal glands, spleen and kidney. In renal hypertensive rats no important changes in tissue dispostion were found, but the apparent volume of distribution of ('125)I-tonin was reduced. ('125)I-PMS-tonin, a modified protein which does not bind to the tonin-inhibitor in plasma, had a significantly different disposition, accumulating in the kidneys, while much less was found in the adrenal glands. When unlabeled tonin was co-injected with ('125)I-tonin, survival of tonin radioactivity in the circulation was prolonged and liver, spleen and adrenal uptake significantly reduced. Co-injection with trypsin produced similar effects, but associated with important hemodynamic changes which might explain the findings. Taken together, these facts suggest that tissue uptake of the tonin-inhibitor complex may be mediated by recognition sites specific for the complex. Radioautography after injection of ('125)I-tonin to rats showed greater accumulation in the adrenal glomerulosa and reticularis. The grains seemed to associate with adrenal cells and not with endothelial cells lining the sinusoids. In the liver the radioautographic reaction was found to concentrate in Kupffer cells. In the kidney grains predominated in the lumenal pole of cells of the proximal convoluted tubule. / A pressor effect of tonin, absent in normal rats or rabbits, was found in bilaterally nephrectomized animals. No important change in vascular reactivity or in the inhibitory power of plasma could be detected. The response was produced by generation of angiotensin II in plasma. A role of substrate levels in the modulation of tonin activity in vivo even in the presence of the tonin inhibitor was suggested. / The infusion of tonin into conscious seemingly unstressed rats produced an increase in plasma aldosterone and corticosterone, and a decrease in plasma renin activity. Plasma angiotensin II concentration was not different from controls, but the plasma renin/angiotensin II ratio was decreased. Plasma electrolytes were unchanged. The angiotensin III antagonist blocked the response of the adrenal. Of angiotensin II antagonists, sar('1)ala('8)angiotensin II was ineffective and sar('1)thr('8)angiotensin II blocked the effect partially. No significant response could be found in sodium depleted rats. The plasma aldosterone concentration in these rats, however, presented a wide dispersion of values. No adrenal response was seen in chronically hypophysectomized rats. Tonin stimulated aldosterone biosynthesis by isolated rat adrenal glomerulosa cells only in the presence of plasma, when large amounts of angiotensin II were generated in the incubate. These results suggest that tonin does not act in vivo directly on adrenal cells. The lack of effect in hypophysectomized rats indicates that the response may be mediated by a pituitary peptide, unless this finding is caused by the reduction of the concentration of substrate in plasma and tissues observed in this experimental situation. / The elevated blood pressure of one-kidney one-clip hypertensive rabbits was reduced when active immunization against tonin was successful. Together with previous evidence, this suggests an involvement of the tonin-angiotensin II system in this form of experimental hypertension.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.77083 |
| Date | January 1980 |
| Creators | Schiffrin, Ernesto Luis. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Experimental Medicine) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000092293, proquestno: AAINK52116, Theses scanned by UMI/ProQuest. |
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