Systemic and regional haemodynamic interactions between K+ channel openers and the sympathetic nervous system in the pithed SHR.
1. The interactions between two K+ channel openers, cromakalim and SR 44866 (infused i.v. at equihypotensive doses), and the sympathetic nervous system at the systemic and regional (mesentery, kidney, hindlimb) vascular levels were investigated in the pithed spontaneously hypertensive rat (SHR) by use of the pulsed Doppler technique. 2. The two K+ channel openers did not affect postsynaptic alpha 1- but slightly reduced postsynaptic alpha 2-adrenoceptor mediated systemic pressor and regional vasoconstrictor responses. 3. Both drugs significantly decreased the systemic pressor and regional vasoconstrictor responses elicited by spinal cord stimulation. These sympathoinhibitory effects were not homogeneously distributed among the different vascular beds, the decreasing rank order being: mesentery greater than kidney greater than hindlimb. Simultaneously, the spinal cord stimulation-induced tachycardia remained unaffected. 4. After treatment with K+ channel openers, restoration of initial blood pressure and vascular tone values by infusion of prostaglandin F2 alpha (PGF2 alpha) and vasopressin respectively did not affect and abolished the sympathoinhibitory effects of cromakalim and SR 44866. 5. We conclude that in SHRs the two K+ channel openers that we investigated exert similar sympathohibitory effects which affect some vascular beds more than others. These effects are not dependent upon the arterial blood pressure level and are most likely prejunctionally located.
Richer
C
C
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France.
Mulder
P
P
Doussau
M P
MP
Gautier
P
P
Giudicelli
J F
JF
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D019806:Cromakalim; D003655:Decerebrate State; D004095:Dihydropyridines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012039:Regional Blood Flow / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D001578:Benzopyrans; D004095:Dihydropyridines; D007093:Imidazoles; D015221:Potassium Channels; D011758:Pyrroles; D011810:Quinoxalines; D019806:Cromakalim; C061050:bimakalim; D000068438:Brimonidine Tartrate; C014282:cirazoline