Effect of Brain Angiotensin II Receptor Antagonists and Antisense Oligonucleotide on Drinking and Renal Renin in Rats

The physiological roles of brain angiotensin II in mediating water deprivation-induced drinking and in regulating renal renin release were assessed in male Sprague-Dawley rats. Specific $AT_1$ receptor antagonists, losartan and SK 1080, and antisense oligonucleotide (AS-ODN) directed to $AT_1$ receptor mRNA were intracerebroventricularly (i.c.v.) administered in conscious unrestrained rats. When water was given 20 min after i.c.v. injection of $AT_1$ receptor antagonists in 48-h water-deprived rats, losartan and SK 1080 produced approximatly 20% and 50% decrease in 1-h water intake, respectively. In contrast, i.c.v. treatment of the AS-ODN to $AT_1$ receptor mRNA for 24-h did not alter 1-h water intake in 24-h water-deprived rats, but prevented the increase in overnight water intake after 24-h water-deprivation. Six-day i.c.v. treatment of AS-ODN did not alter either the basal plasma renin concentration or renal cortical levels of renin and renin mRNA. The present results suggest that endogenous brain Ang II plays an important role in thirst and water intake through $AT_1$ receptors, but further studies are required to elucidate its regulatory role in renal renin synthesis.