Chronic low-dose angiotensin II infusion increases venomotor tone by neurogenic mechanisms.
The purpose of this study was to identify changes in venomotor tone in the chronic low-dose angiotensin II (Ang II) model of hypertension and to establish the contribution of sympathetic nerve activation to these venomotor tone changes. Male Sprague-Dawley rats were acclimatized to a 0.4% or 2.0% NaCl diet for 7 days and then catheterized to allow chronic and repeated measures of arterial pressure, central venous pressure, and mean circulatory filling pressure (MCFP), an index of venous smooth muscle tone, in conscious undisturbed rats. After 4 days of recovery and a 3-day control period, an Ang II or physiological saline-filled osmotic minipump was implanted subcutaneously to deliver Ang II (150 ng/kg per minute) or vehicle control for 14 days. MCFP was measured in duplicate before and after acute ganglionic blockade with hexamethonium (30 mg/kg i.v.) on control day 2 and Ang II infusion on days 1, 3, 7, and 14. Blood volume was also measured on these days and was unchanged for the duration of the study in all of the groups. Arterial pressure was increased for the duration of Ang II infusion in rats on both 0.4% and 2% NaCl diets, but the increase was significantly greater in the 2% NaCl group and completely abolished by hexamethonium. MCFP was significantly increased for the entire Ang II infusion period only in rats fed 2% NaCl, and this increase was completely abolished by hexamethonium. We conclude that the combination of chronic low-dose Ang II infusion and high dietary salt intake engages the sympathetic nervous system to increase venomotor tone.
King
Andrew J
AJ
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Fink
Gregory D
GD
D000804:Angiotensin II / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D014690:Venous Pressure
D017673:Sodium Chloride, Dietary; D000804:Angiotensin II