The amino acid composition of angiotensin alters its ability to reduce alcohol consumption in rats

Abstract

The voluntary consumption of alcohol has been shown to be reduced by a variety of manipulations which enhance activity in the renin-angiotensin system, including the administration of the bovine form of angiotensin II-[Val5]-ANG II. The present study investigated the relationship between the amino acid composition of angiotensin II and its ability to reduce alcohol intake by administering a number of different forms or fragments of the parent peptide. [Ile5]-Angiotensin II ([Ile5]-ANG II), two endogenous fragments of angiotensin II [( Des-Asp1]-ANG II and [Des-Phe8]-ANG II) were administered subcutaneously in rats across a range of doses. [Ile5]-ANG II reduced alcohol intake at all doses tested between 20 and 400 micrograms/kg while [Des-Asp1]-ANG II reduced alcohol intake only at the 400 micrograms/kg dose. [Des-Phe8]-ANG II had no effect on alcohol intake at any dose tested. Administration of the antagonist [Sar1-Thr8]-ANG II by itself did not enhance alcohol intake. While the pressor and dipsogenic properties of these fragments sometimes correlated with the reduction in alcohol intake they were not a causal factor in decreasing the intake. These results indicate that variations in the peptide composition of angiotensin can significantly alter its ability to reduce the consumption of alcohol.