Cardiovascular and adrenaline-releasing effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin in streptozotocin diabetic rats.
The 5-hydroxytryptamine1A (5-HT1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) has been reported to trigger sympathoinhibition, as evidenced by its cardiovascular effects, and adrenal catecholamine secretion. The purpose of this study was to analyze the cardiovascular and adrenaline-releasing effects of 8-OH-DPAT in 1 week streptozotocin diabetic rats. 8-OH-DPAT-induced changes in mean arterial pressure (MAP) and heart rate (HR) were determined directly in anesthetized rats, whilst changes in plasma adrenaline (and plasma corticosterone and glucose) levels were analyzed in conscious rats. Resting blood pressure and heart rate were diminished in diabetics, when compared with controls. These changes were associated with a decrease in body weight and a marked increase in resting plasma glucose levels. Diabetes did not affect MAP response to 8-OH-DPAT, except for a decrease in the amplitude of MAP maximal fall, which was associated with a diminished bradycardic response to 8-OH-DPAT. Blood pressure response to prazosin (0.5 mg/kg) in 8-OH-DPAT-pretreated rats was also diminished in diabetics. Lastly, diabetes prevented the adrenaline-releasing and hyperglycemic effects of 8-OH-DPAT (250 ug/kg).
Chaouloff
F
F
Laboratoire de Pharmacologie, CNRS, CHU Necker-EM, Paris, France.
Blanc
J
J
Baudrie
V
V
Laude
D
D
Elghozi
J L
JL
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D013311:Streptozocin / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D001786:Blood Glucose; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D013311:Streptozocin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003345:Corticosterone; D004837:Epinephrine