ANTIHYPERTENSIVE EFFECTS OF 2-OCTYNYLADENOSINE (YT-146), A SELECTIVE ADENOSINE A(2) RECEPTOR AGONIST, IN DAHL SALT-SENSITIVE RATS

被引：9

作者：

IWAMOTO, T ^{[1
]}

UMEMURA, S ^{[1
]}

TOYA, Y ^{[1
]}

HIRAWA, N ^{[1
]}

TAKEDA, K ^{[1
]}

KIHARA, M ^{[1
]}

ISHII, M ^{[1
]}

机构：

[1] YOKOHAMA CITY UNIV,SCH MED,DEPT INTERNAL MED 2,KANAZAWA KU,YOKOHAMA,KANAGAWA 236,JAPAN

来源：

AMERICAN JOURNAL OF HYPERTENSION | 1994年 / 7卷 / 11期

关键词：

ADENOSINE RECEPTOR AGONIST; 2-OCTYNYLADENOSINE; ANTIHYPERTENSIVE AGENT; DAHL SALT-SENSITIVE RAT;

D O I：

10.1093/ajh/7.11.984

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

The antihypertensive effects of a novel adenosine A(2) 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. In the chronic study, neither PRA, plasma ADH concentration, urinary volume, urinary excretion of Na and K, nor creatinine clearance were affected, although plasma ANP concentration was significantly lowered (176 +/- 35 v 73 +/- 20 pmol/ mL, P < .05) by 1.0 mg/kg of YT-146, compared with vehicle-treated rats. These data indicate that orally administered YT-146 shows antihypertensive effects without reflex tachycardia and has no remarkable effect on renal function in an animal model of hypertension.

引用

页码：984 / 988

页数：5

共 27 条

[1]

Collis M.G., Brown C.M., Adenosine relaxes the aorta by interacting with an A2 receptor and an intracellular site, Eur J Pharmacol, 96, pp. 61-69, (1983)

[2]

Mustafa S.J., Askar A.O., Evidence suggesting an Ra-type adenosine receptor in bovine coronary arteries, J Pharmacol Exp Ther, 232, pp. 49-56, (1985)

[3]

Evans D.B., Schenden J.A., Bristol J.A., Adenosine receptor mediated cardiac depression, Life Sci, 31, pp. 2425-2432, (1982)

[4]

Hughs P.R., Stone T.W., Inhibition by purines of the inotropic action of isoprenaline in rat atria, Br J Pharmacol, 80, pp. 149-153, (1983)

[5]

Dunwiddie T.V., The physiological role of adenosine in the central nervous system, Int Rev Neurobiol, 27, pp. 63-139, (1985)

[6]

Dobson J.G., Fenton R.A., Romano F.D., The antiadrenergic actions of adenosine in the heart, pp. 356-368, (1987)

[7]

Hattori Y., Levi R., Adenosine selectivity attenuates H2- and β-mediated cardiac responses to histamine and norepinephrine: An unmasking of H1- and β-mediated cardiac responses, J Pharmacol Exp, 231, pp. 215-223, (1984)

[8]

Fredholm B., Dunwiddie T.V., How does adenosine inhibit neurotransmitter release?, Trends Pharmacol Sci, 9, pp. 130-134, (1988)

[9]

Van Calker D., Muller D.M., Hamprecht B., Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cell, J Neu-Rochem, 33, pp. 999-1005, (1979)

[10]

Stiles G.L., Adenosine receptors. Structure, function and regulation, Trends Pharmacol Sci, 7, pp. 486-490, (1986)

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