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)
Second Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
T
T
Iwamoto
S
S
Umemura
Y
Y
Toya
N
N
Hirawa
K
K
Takeda
M
M
Kihara
M
M
Ishii
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