Total peripheral conductance mediates antihypertensive effect of nonpeptide mixed endothelin receptor antagonist in deoxycorticosterone acetate-salt hypertensive rats. 1999

M Yu, and V Gopalakrishnan, and J R McNeill
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.

The relative contribution of cardiac output (CO) and total peripheral conductance (TPC) to the changes in blood pressure (BP) evoked by an intravenous injection of bosentan, a nonpeptide mixed endothelin (ET) antagonist, were investigated in conscious unrestrained deoxycorticosterone acetate (DOCA)-salt hypertensive rats and sham-control rats. Blood pressure was recorded by radiotelemetry devices and CO by ultrasonic transit-time flow probes. Bosentan significantly reduced BP (from 141 +/- 3 to 111 +/- 3 mm Hg) and increased TPC (from 1.19 +/-0.1 to 1.72 +/- 0.2 mL/min/kg/mm Hg) in DOCA-salt hypertensive rats, but not in sham rats. An increase in CO opposed the BP-lowering effect of the antagonist. The results demonstrate that the role of ET receptors in the maintenance of the hypertensive state in the DOCA-salt model of hypertension is exerted at the level of the resistance vessels and not on factors that regulate cardiac output.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D008297 Male Males
D012039 Regional Blood Flow The flow of BLOOD through or around an organ or region of the body. Blood Flow, Regional,Blood Flows, Regional,Flow, Regional Blood,Flows, Regional Blood,Regional Blood Flows
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002302 Cardiac Output The volume of BLOOD passing through the HEART per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with STROKE VOLUME (volume per beat). Cardiac Outputs,Output, Cardiac,Outputs, Cardiac
D003900 Desoxycorticosterone A steroid metabolite that is the 11-deoxy derivative of CORTICOSTERONE and the 21-hydroxy derivative of PROGESTERONE 21-Hydroxyprogesterone,Cortexone,Deoxycorticosterone,Desoxycortone,11-Decorticosterone,21-Hydroxy-4-pregnene-3,20-dione,11 Decorticosterone,21 Hydroxy 4 pregnene 3,20 dione,21 Hydroxyprogesterone
D000077300 Bosentan A sulfonamide and pyrimidine derivative that acts as a dual endothelin receptor antagonist used to manage PULMONARY HYPERTENSION and SYSTEMIC SCLEROSIS. 4-t-Butyl-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl)benzenesulfonamide,Bosentan Anhydrous,Bosentan Monohydrate,Ro 47-0203,Ro-47-0203,Tracleer,Ro 47 0203,Ro 470203
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000959 Antihypertensive Agents Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. Anti-Hypertensive,Anti-Hypertensive Agent,Anti-Hypertensive Drug,Antihypertensive,Antihypertensive Agent,Antihypertensive Drug,Anti-Hypertensive Agents,Anti-Hypertensive Drugs,Anti-Hypertensives,Antihypertensive Drugs,Antihypertensives,Agent, Anti-Hypertensive,Agent, Antihypertensive,Agents, Anti-Hypertensive,Agents, Antihypertensive,Anti Hypertensive,Anti Hypertensive Agent,Anti Hypertensive Agents,Anti Hypertensive Drug,Anti Hypertensive Drugs,Anti Hypertensives,Drug, Anti-Hypertensive,Drug, Antihypertensive,Drugs, Anti-Hypertensive,Drugs, Antihypertensive

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