Antihypertensive effects of 2-octynyladenosine (YT-146), a selective adenosine A2 receptor agonist, in Dahl salt-sensitive rats.
The antihypertensive effects of a novel adenosine A2 receptor agonist, 2-octynyl adenosine (YT-146), were evaluated in Dahl salt-sensitive rats. After rats were fed a high-salt (8% NaCl) diet for 2 or 3 weeks, they received oral YT-146 (0.1 or 1.0 mg/kg) or vehicle as a single dose (acute study) or once daily for 10 days (chronic study). In the acute study, tail-cuff blood pressure (BP) and pulse rate (PR) were measured before and 3, 6, and 24 h after administration, and blood samples were collected 3 h after administration. In the chronic study, BP and PR were measured 3 and 24 h after administration and urine was collected for 24 h on day 9. Blood samples were also collected 3 h after administration on day 10. BP was significantly lowered by 1.0 mg/kg of YT-146 in either the acute study (from 184 +/- 3 to 152 +/- 5 mm Hg, P < .01) or the chronic study (from 226 +/- 4 to 201 +/- 2 mm Hg, P < .01), while an increase in PR was not observed (acute study: from 382 +/- 8 to 366 +/- 3 beats/min; chronic study: from 420 +/- 8 to 411 +/- 8 beats/min). YT-146 had no effect on plasma renin activity (PRA), plasma aldosterone, vasopressin (ADH), and atrial natriuretic peptide (ANP) in the acute study.(ABSTRACT TRUNCATED AT 250 WORDS)
Iwamoto
T
T
Second Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Umemura
S
S
Toya
Y
Y
Hirawa
N
N
Takeda
K
K
Kihara
M
M
Ishii
M
M
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000284:Administration, Oral; D000480:Alkynes / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D011674:Pulse / Q000187:drug effects; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D011919:Rats, Inbred Strains
D000480:Alkynes; D000959:Antihypertensive Agents; D058906:Purinergic P1 Receptor Agonists; C070494:YT 146; D000241:Adenosine