Salt-dependency of endothelin-induced, chronic hypertension in conscious rats.
The effect of salt intake on the hypertensive response to long-term infusion of endothelin-1 was investigated. Chronically instrumented male Sprague-Dawley rats (325-375 g) were used in a 15-day protocol that included 3 control days followed by 7 days of endothelin-1 infusion at 5.0 pmol.kg-1.min-1 and 5 days of recovery. Rats were maintained on either a normal sodium chloride intake (2.0 meq Na+ per day; normal sodium) or a high sodium chloride intake (6.0 meq Na+ per day; high sodium) throughout the protocol. Control rats received normal or high sodium intakes but not endothelin-1. In high-sodium rats, endothelin-1 produced a significant increase in mean arterial pressure and total peripheral resistance; a significant bradycardia was observed only on the first day after the start of the endothelin-1 infusion. Cardiac output, stroke volume, water balance, and urinary sodium and potassium excretion remained unchanged. Termination of endothelin-1 infusion resulted in rapid normalization of both arterial pressure and peripheral resistance. In contrast, normal sodium rats exhibited no alteration in mean arterial pressure, heart rate, total peripheral resistance, stroke volume, water balance, or urinary sodium and potassium excretion throughout the endothelin-1 infusion protocol. The hypertension produced by endothelin-1 infusion cannot be explained by alterations in salt or water balance since endothelin-1 infusion in high sodium animals produced significant increases in mean arterial pressure with no observable changes in water or electrolyte balance. These results indicate that endothelin-induced hypertension in conscious rats is a salt-dependent model of hypertension.
Mortensen
L H
LH
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Fink
G D
GD
D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D002908:Chronic Disease; D016232:Endothelins; D006973:Hypertension / Q000139:chemically induced* / Q000652:urine; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology*
D016232:Endothelins; D012965:Sodium Chloride