Opposite influences of hypertension and diabetes mellitus on pressor responses induced by different alpha-adrenoceptor agonists and angiotensin II in pithed rats.
Hypertension is often present in the diabetic individual and it is known to aggravate the vascular complications associated with diabetes. The pressor responses to two alpha 1-adrenoceptor agonists (ST587 and cirazoline), two alpha 2-adrenoceptor agonists (azepexole dihydrochloride (B-HT933) and UK14.304) and angiotensin II were investigated in pithed spontaneously hypertensive rats (SHR) and in pithed normotensive Wistar Kyoto rats (WKY) made diabetic by a single i.v. injection (55 mg/kg) of streptozotocin (STZ). Two months after diabetes was induced, the effect of the agonists on basal diastolic blood pressure (DBP) was determined. In pithed diabetic WKY and SHR, the maximal pressor response was impaired for all agonists. The dose response curves were shifted to the right when compared with their non-diabetic controls. The hypertensive state enhanced the maximal pressor response to all agonists compared with non-hypertensive animals. Additional diabetes blunted this increase in the effects of ST587, B-HT933 and angiotensin II, but not in those of cirazoline and UK14.304. Hypertension caused a leftward shift of the dose response curve for ST587 when compared with the non-hypertensive state. However, this effect was not observed when diabetes was present as well. In conclusion, hypertension resulted in an enhanced pressor effect, possibly caused by vascular hypertrophy, whereas the diabetic state counteracted this effect.
Beenen
O H
OH
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
Mathy
M J
MJ
Pfaffendorf
M
M
van Zwieten
P A
PA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects*; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003655:Decerebrate State; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D001786:Blood Glucose; D007093:Imidazoles; D011810:Quinoxalines; D000804:Angiotensin II; C030655:St 587; D000068438:Brimonidine Tartrate; C015603:azepexole; D003000:Clonidine; C014282:cirazoline