Antihypertensive,vasodilating, and sympatholytic activities of ofornine® in spontaneously hypertensive rats |
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Authors: | Albert Defelice Harlan Lape Patrick Horan Richard Frering Armand Brousseau Bernard O'Connor John Herrmann Denis Bailey |
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Abstract: | This study of spontaneously hypertensive (SH) rats documents oral antihypertensive activity of the vasodilator Ofornine®, an anthranilamide whose effect was sustained, at least in part, by suppression of compensatory renal and neurohumoral responses. Doses of 2.5 to 100 μg/kg p.0. reduced systolic blood pressure (BP) by up to 75 mm Hg. Effect lasted 6-24 hr and did not diminish during a 16 day (25 μg/kg/day) regimen. Metoclopramide (10.0 μg/kg)and haloperidol (3.0 μg/kg) antagonized the antihypertensive effect. Antihypertensive activity was confirmed by direct (arterial cannula) monitoring where 0.001-1.O μg/kg i.v. reduced mean BP by 6-47% without tachycardia. Doses of 1-10 ag/kg i.a. reduced perfusion pressure of the SH rat hindquarters by 35-74 mm Hg. A dose of 5.0 μg/kg p.0. reduced BP and urine norepinephrine levels of SH rats by 58 mm Hg and approximately 50% without raising plasma renin activity or causing sodium retention. How- ever, Ofornine® (25 μg/kg p.0. daily for 6 days) did not affect reflex bradycardic or tachy- cardic effects of phenylephrine and sodium nitroprusside in SH rats. These and other results indicate that Ofornine@ reduces SH rat blood pressure through vasodilating and presynaptic adrenolytic activities, and that a dopaminergic mechanism may be involved. |
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Keywords: | potential antihypertensive presynaptic adrenolytic sympatholytic vasodilator SH rats |
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