Dysfunctional presynaptic alpha 2-adrenoceptors expose facilitatory beta 2-adrenoceptors in the vasculature of spontaneously hypertensive rats.
Previous studies on spontaneously hypertensive rats (SHR) have yielded inconsistent information about functional aberrations of the presynaptic alpha 2- and beta 2-adrenoceptor-mediated modulation of sympathetic neurotransmitter release. In the present investigation we studied the capacity of presynaptic beta 2-adrenoceptors that enhance noradrenaline (NA) release in the portal vein of freely moving, unanesthetized SHR and normotensive Wistar rats (WR) using the beta 2-selective agonist fenoterol. The results show that the presynaptic beta 2-adrenoceptor population in SHR responds to significantly lower dosages of fenoterol than that in WR. The reason for this enhanced action, however, could not be attributed to the beta 2-adrenoceptor itself, nor to a diminished neuronal uptake of NA, but to a diminished responsiveness of the presynaptic alpha 2-adrenoceptor. Stimulation of presynaptic alpha 2-adrenoceptors with oxymetazoline (45 micrograms/min) decreased basal NA levels by 46% in WR and by 3% in SHR. Blockade of alpha 2-adrenoceptors, using 0.5 mg/kg yohimbine, induced a 4.86-fold rise in the basal NA level in WR but only a 1.89-fold rise in SHR. A subsequent dose of fenoterol, however, resulted in a further 2.5- and 2.6-fold rise in WR and SHR, respectively, indicating that there is a normal presynaptic beta 2-adrenoceptor population in the vasculature of SHR.
Remie
R
R
Department of Pharmacology and Therapeutics, University of Groningen, The Netherlands.
Van Rossum
J X
JX
Coppes
R P
RP
Zaagsma
J
J
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D005280:Fenoterol / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D010109:Oxymetazoline / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D005280:Fenoterol; D015016:Yohimbine; D010109:Oxymetazoline; D003042:Cocaine; D009638:Norepinephrine