Pharmacology of eprosartan, an angiotensin II receptor antagonist: exploring hypotheses from clinical data.
Selective blockade of the angiotensin II AT1 receptor represents a novel mechanism for interrupting the renin-angiotensin system without altering the potential benefits of AT2 receptor stimulation. This selective inhibition produces none of the disadvantages associated with reduced bradykinin metabolism and angiotensin II generated by non-angiotensin-converting enzyme pathways. Eprosartan is a potent (1.4 nmol/L) AT1 receptor antagonist that competitively blocks angiotensin II-induced vascular contraction. In various animal models of disease, including hypertension and stroke, eprosartan is effective in reducing disease progression. Eprosartan also has sympathoinhibitory activity, as demonstrated by an inhibition of the pressor responses induced by activation of sympathetic outflow through spinal cord stimulation in pithed rats. In contrast, some of the other angiotensin II receptor antagonists, such as losartan, at equivalent angiotensin II blocking doses, have no effect on sympathetic nervous system activity. Because eprosartan can inhibit both the direct effects of angiotensin II as well as the indirect effects that are mediated by enhanced sympathetic neurotransmission, this may represent an important advance in the treatment of elevated systolic blood pressure.
Brooks
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DP
SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-2799, USA.
Ohlstein
E H
EH
Ruffolo
R R
RR
D000179:Acrylates / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000517:prevention & control; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000494:pharmacology*; D051381:Rats; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D013876:Thiophenes
D000179:Acrylates; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013876:Thiophenes; D000804:Angiotensin II; C068373:eprosartan