Hypoglycemic and hypotensive effects of 6-cyclohexyl-2'-O-methyl-adenosine, an adenosine A1 receptor agonist, in spontaneously hypertensive rat complicated with hyperglycemia.
Metabolic and cardiovascular effects of 6-cyclohexyl-2'-O-methyl-adenosine (SDZ WAG 994), a selective and orally-active adenosine A1 receptor agonist, were examined in spontaneously hypertensive rats (SHR) with hyperglycemia (SHR-DM). This model was made by the administration of streptozotocin (STZ; 60 mg/kg s.c.) to SHR 2 days after their birth. The serum glucose concentration and systolic/mean blood pressures (MBP) in 18-22-week-old rats were 14.7 +/- 0.8 mmol/1 and 153 +/- 3/124 +/- 3 mmHg in SHR-DM, 13.7 +/- 0.3 mmol/1 and 123 +/- 3/96 +/- 4 mmHg in normotensive with STZ (WKY-DM), 10.3 +/- 0.3 mmol/1 and 165 +/- 1/136 +/- 3 mmHg in non-treated (without STZ) SHR, and 10.0 +/- 0.3 mmol/1 and 115 +/- 3/90 +/- 4 mmHg in non-treated WKY, SDZ WAG 994 at 0.1 mg/kg p.o. lowered the serum glucose concentration, blood pressure and heart rate in SHR-DM. The effects were associated with the decrease in free fatty acid (FFA), triglyceride (TG), phospholipid (PL) and total cholesterol (TC) in serum of both SHR-DM and WKY-DM. On the contrary, the hypoglycemic effect was not found in WKY-DM, although the hypotensive effect was still observed. These data suggest that the risk factors for metabolic and cardiovascular complications in diabetes are reduced by SDZ WAG 994 through activation of adenosine A1 receptors in adipocyte.
Ishikawa
J
J
Department of Pharmacology, Sandoz Tsukuba Research Institute, Ibaraki, Japan. Junji.Ishikawa@novartis.com
Mitani
H
H
Bandoh
T
T
Kimura
M
M
Totsuka
T
T
Hayashi
S
S
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006943:Hyperglycemia / Q000150:complications* / Q000503:physiopathology; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology; D007003:Hypoglycemia / Q000139:chemically induced*; D007022:Hypotension / Q000139:chemically induced*; D008055:Lipids / Q000097:blood; D008297:Male; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013311:Streptozocin / Q000494:pharmacology
D001786:Blood Glucose; D008055:Lipids; D058906:Purinergic P1 Receptor Agonists; C090949:N(6)-cyclohexyl-2-O-methyladenosine; D013311:Streptozocin; D000241:Adenosine