Hormonal and Cardiovascular Effects of Losulazine Hydrochloride in Relation to Sodium Balance in Nonhuman Primates

Abstract

Losulazine hydrochlonde, a peripheral norepinephrine-depleting agent, was studied in conscious sodium-replete and sodium depleted cynomolgus monkeys. Blood pressure, heart rate, plasma renin activity, and plasma catecholamines were monitored before and after the oral administration of losulazine at a dose which caused a submaximal hypotension in sodium-replete monkeys.The hypotension observed in both sodium depleted monkeys was not significantly different from that observed in sodium-replete monkeys. The hypotension observed in both sodium states was accompanied by quantitatively similar decreases in plasma norepinephrine concentrations in the absence of significant alterations of heart rate and plasma renin activity. These results were consistent with the conclusion that losulazine reduced arterial blood pressure in nonhuman primates via peripheral norepinephrine depletion. These data also indicated that the hypotensive effect of losulazine in conscious monkeys was not dependent on alterations in renin angiotensin system activity or on the state of sodium balance.

Key Words:

• Renin
• Norepinephrine
• Sodium balance
• Blood pressure
• Cynomolgus monkey