Mechanisms of increased venous smooth muscle tone in desoxycorticosterone acetate-salt hypertension.
The purpose of the present study was to identify mechanisms that contribute to increased venous smooth muscle tone in desoxycorticosterone acetate (DOCA)-salt hypertension in rats. Male Sprague-Dawley rats were uninephrectomized, received subcutaneous implants of DOCA, and drank 1% sodium chloride/0.2% potassium chloride solutions. Sham-operated rats received only uninephrectomy and drank tap water. Three to 4 weeks later, arterial and venous catheters were implanted for measurements of arterial and central venous pressures, respectively, and a silicone balloon catheter was permanently fixed in the right atrium to produce brief circulatory arrest. Venous smooth muscle activity was estimated on the basis of repeated measurements of mean circulatory filling pressure in conscious rats resting in their home cages. DOCA-salt-treated rats were hypertensive and had elevated mean circulatory filling pressure compared with normotensive sham-operated rats. Blockade of the endothelin subtype A receptor with 1 mg/kg ABT-627 IV decreased arterial blood pressure and mean circulatory filling pressure significantly more in hypertensive rats than in normotensive rats. Ganglionic blockade with 30 mg/kg hexamethonium IV also decreased arterial blood pressure and mean circulatory filling pressure more in hypertensive than in normotensive rats. Pretreatment with ABT-627 did not affect subsequent hemodynamic responses to ganglionic blockade. We conclude that venous smooth muscle tone is increased in DOCA-salt hypertension through the independent actions of both endogenous endothelin-1 acting on subtype A receptors and sympathetically mediated venoconstrictor activity.
Fink
G D
GD
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824-1317, USA. finkg@pilot.msu.edu
Johnson
R J
RJ
Galligan
J J
JJ
D000818:Animals; D000077868:Atrasentan; D001810:Blood Volume; D003243:Consciousness; D003900:Desoxycorticosterone; D065128:Endothelin Receptor Antagonists; D005730:Ganglionic Blockers / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007601:Jugular Veins / Q000737:chemistry / Q000294:innervation / Q000502:physiology*; D008297:Male; D009129:Muscle Tonus / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D005730:Ganglionic Blockers; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D017673:Sodium Chloride, Dietary; D018738:Hexamethonium; D003900:Desoxycorticosterone; D000077868:Atrasentan