Time course of losartan blockade of angiotensin II hypertension versus blockade of angiotensin II fast pressor effects. 1994

V J Gorbea-Oppliger, and M G Melaragno, and G S Potter, and R L Petit, and G D Fink
Department of Pharmacology and Toxicology, Michigan State University, East Lansing.

This study investigated the ability of the selective angiotensin II (AII)-type (AT)1 receptor antagonist losartan to reverse the fast (< 30 sec) pressor effect of AII, and the hypertension produced by chronic (2 weeks) i.v. infusion of AII (AII hypertension). We hypothesized the following: if AII hypertension is caused solely by stimulation of AT1 receptors mediating the fast pressor effect, then the time course of the antihypertensive effect of losartan in AII hypertension should parallel the time course of losartan inhibition of pressor responses to acute, bolus injection of AII. Thus, in one group of rats, pressor responses to bolus injections of AII (10 ng, n = 10) were measured before and subsequently at numerous time points after losartan administration (3 mg.kg-1 i.v.). Other groups of rats received continuous infusions of AII i.v. for 15 days at 2 ng.min-1 (n = 8), 4 ng.min-1 (n = 8) or 10 ng.min-1 (n = 6). On days 2, 7 and 12 of the AII infusion, rats received a bolus injection of losartan (3 mg.kg-1, i.a.). Mean arterial pressure (MAP) was then measured at numerous time points after losartan administration. Within 5 min of administration, losartan caused almost complete inhibition of fast pressor responses to acute injections of AII, and the magnitude of this inhibition did not change for over 24 hr. On the other hand, in AII hypertension, losartan lowered MAP significantly within 5 min only in rats receiving 10 ng.min-1 AII, but in all three groups caused a slower decline in MAP that peaked around 2 hr after losartan injection.(ABSTRACT TRUNCATED AT 250 WORDS)

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
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D008297 Male Males
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
D001933 Brain Stem The part of the brain that connects the CEREBRAL HEMISPHERES with the SPINAL CORD. It consists of the MESENCEPHALON; PONS; and MEDULLA OBLONGATA. Brainstem,Truncus Cerebri,Brain Stems,Brainstems,Cerebri, Truncus,Cerebrus, Truncus,Truncus Cerebrus
D006339 Heart Rate The number of times the HEART VENTRICLES contract per unit of time, usually per minute. Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse
D000804 Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS. Angiotensin II, Ile(5)-,Angiotensin II, Val(5)-,5-L-Isoleucine Angiotensin II,ANG-(1-8)Octapeptide,Angiotensin II, Isoleucine(5)-,Angiotensin II, Valine(5)-,Angiotensin-(1-8) Octapeptide,Isoleucine(5)-Angiotensin,Isoleucyl(5)-Angiotensin II,Valyl(5)-Angiotensin II,5 L Isoleucine Angiotensin II,Angiotensin II, 5-L-Isoleucine
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
D001713 Biphenyl Compounds Whitish aromatic crystalline organic compounds made up of two conjoined BENZENE rings. Compounds, Biphenyl

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