Some Contributions to the Pharmacology of Synthetic Angiotensin
The examination of synthetic valyl-5-angiotensin II-amide in the conscious dog revealed the following:
1. Both the arterial and the central venous pressure responses exhibit tachyplylaxis when high doses of angiotensin II are administered, althoug not when medium or low doses are given. Cross-tachyphylaxis can be demonstrated between renin and angiotensin II but not between either of these and norepinephrine. These results suggest that tachyphylaxis to renin is due to tachyphylaxis to angiotensin.
2. Angiotensin II and norepinephrine provoke a dose-dependent increase in central venous pressure. The threshold dose is about 10 times higher than that necessary for the effect on arterial pressure. In doses eliciting the same increase of arterial blood pressure, norepinephrine is about twice as active on the venous pressure as angiotensin II.
3. Anesthesia and atropinization both reduce or abolish the effect of angiotensin II as well as that of norepinephrine on the venous pressure, indicating the reflex nature of the underlying mechanism.
4. In endotoxin hypotension, the pressor response to angiotensin II and to norepinephrine is diminished, and the venous pressure response becomes gradually depressed until it is completely abolished.
5. During hemorrhagic hypotension, the response to angiotensin II may be retained or even enhanced and is less likely to have an adverse effect on the myocardium than norepinephrine.
- © 1962 American Heart Association, Inc.