HYPOGLYCEMIC AND HYPOTENSIVE EFFECTS OF 6-CYCLOHEXYL-2'-O-METHYL-ADENOSINE, AN ADENOSINE A(1) RECEPTOR AGONIST, IN SPONTANEOUSLY HYPERTENSIVE RAT COMPLICATED WITH HYPERGLYCEMIA

Metabolic and cardiovascular effects of 6-cyclohexyl-2'-O-methyl-adeno sine (SDZ WAG 994), a selective and orally-active adenosine A(1) recep tor agonist, were examined in spontaneously hypertensive rats (SHR) wi th hyperglycemia (SHR-DM). This model was made by the administration o f streptozotocin (STZ; 60 mg/kg s.c.) to SHR 2 days after their birth. The serum glucose concentration and systolic/mean blood pressures (MB P) in 18-22-week-old rats were 14.7 +/- 0.8 mmol/l and 153 +/- 3/124 /- 3 mmHg in SHR-DM, 13.7 +/- 0.3 mmol/l and 123 +/- 3/96 +/- 4 mmHg i n normotensive with STZ (WKY-DM), 10.3 +/- 0.3 mmol/l and 165 +/- 1/13 6 +/- 3 mmHg in non-treated (without STZ) SHR, and 10.0 +/- 0.3 mmol/l 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 h eart rate in SHR-DM. The effects were associated with the decrease in foe fatty acid (FFA), triglyceride (TG), phospholipid (PL) and total c holesterol (TC) in serum of both SHR-DM and WKY-DM. On the contrary, t he hypoglycemic effect aias not found in WKY-DM, although the hypotens ive effect was still observed. These data suggest that the risk factor s for metabolic and cardiovascular complications in diabetes are reduc ed by SDZ WAG 994 through activation of adenosine A(1) receptors in ad ipocyte. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.