Influence of nifedipine on pressor responses induced by different alpha-adrenoceptor agonists and angiotensin II in pithed diabetic hypertensive rats.
OBJECTIVE
Both intracellular and extracellular sources of calcium are involved in the activation of contraction in vascular smooth muscle. In the diabetic or hypertensive state, or both, changes induced in calcium handling by various types of agonists may vary considerably.


METHODS
We investigated in which manner L-type calcium-channel blockade with nifedipine influences the pressor effects of the alpha 1-adrenoceptor agonists cirazoline and ST 587, the alpha 2-adrenoceptor agonist UK 14.304 and angiotensin II, all exerting a differential influence on calcium homeostasis, in pithed spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats rendered diabetic by an injection of 55 mg/kg streptozotocin.


RESULTS
In diabetic WKY rats and SHR, the maximal pressor response was impaired for all agonists. The hypertensive state enhanced the maximal pressor response to all agonists. No difference was found in the nifedipine-induced depression of the pressor response to cirazoline and angiotensin II in the four groups of rats. The maximal pressor responses to ST 587 and UK 14.304 were more effectively depressed by administration of 0.3 mg/kg nifedipine both in diabetic WKY rats and in diabetic SHR than they were in their non-diabetic controls.


CONCLUSIONS
Hypertension was associated with enhanced pressor response, whereas the diabetic state counteracted this effect. The pressor responses in pithed diabetic and diabetic hypertensive rats were clearly more dependent on the nifedipine-sensitive calcium influx than were those in their non-diabetic controls.
Beenen
O H
OH
Department of Pharmacotherapy, University of Amsterdam, Academic Medical Centre, The Netherlands.
Mathy
M J
MJ
Pfaffendorf
M
M
van Zwieten
P A
PA
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D000068438:Brimonidine Tartrate; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013311:Streptozocin / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D007093:Imidazoles; D011810:Quinoxalines; D000804:Angiotensin II; C030655:St 587; D000068438:Brimonidine Tartrate; D013311:Streptozocin; D009543:Nifedipine; D003000:Clonidine; C014282:cirazoline; D002118:Calcium