The hypotensive effect of an oral adenosine analog with selectivity for the A2 receptor in the spontaneously hypertensive rat.
Adenosine is a potent arterial vasodilator that, because of a short duration of action and acid lability, is ineffective in the oral treatment of hypertension. Y-341 is a synthetic adenosine analog that is acid stable and has a prolonged duration of action. It is highly selective for the A2 receptor, which is prevalent in the vascular smooth muscle and mediates vasodilation. To determine the efficacy of Y-341 as an antihypertensive agent, the effect of Y-341 on arterial pressure was studied in spontaneously hypertensive rats (SHR) in the awake state, 3 to 4 days after arterial cannulation. Y-341 (3 mg/kg) was dissolved in 5% DMSO and administered by gavage. Blood pressure and heart rate were monitored continuously at predetermined intervals. Fifteen minutes after administration, Y-341 reduced MAP from 180 +/- 4 to 126 +/- 2 mm Hg (n = 9, P < .001). There was no significant change in heart rate. The hypotensive effect was sustained over 8 h. Vehicle (n = 5) had no effect on blood pressure. The hypotensive effect was dose dependent when the dose of Y-341 was increased from 3 to 6 and 12 mg/kg. When Y-341 was administered at 3 mg/kg/day in a single dose for 5 consecutive days, there was no significant change in the magnitude of the hypotensive response over time.(ABSTRACT TRUNCATED AT 250 WORDS)
Yagil
Y
Y
Department of Nephrology and Hypertension, Barzilai Medical Center, Ashkelon, Israel.
Miyamoto
M
M
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000378:metabolism
D018047:Receptors, Purinergic P1; C082872:metrifudil; D000241:Adenosine