The function of alpha- and beta-adrenoceptors of the saphenous artery in caveolin-1 knockout and wild-type mice.
OBJECTIVE
Adrenoceptors can associate with cardiac caveolae. To investigate the function of vascular caveolae, adrenoceptor-mediated effects were compared in the saphenous artery of caveolin-1 knockout (cav-1KO) and wild-type (WT) mice.


METHODS
Electronmicroscopy was used to detect caveolae. Real-Time quantitative PCR was used for adrenoceptor subtypes. Catecholamine-evoked contractions and relaxations were studied in arterial segments.


RESULTS
Caveolae were found in arterial smooth muscle from WT but not from cav-1KO mice. Arterial mRNA levels for the adrenoceptors alpha1A, alpha1B, alpha1D, beta1, beta2 and beta3 were similar in cav-1KO and WT. (-)-Noradrenaline contracted cav-1KO (-log EC50M=7.1) and WT (-log EC50M=7.3) arteries through prazosin-sensitive receptors. Maximum (-)-noradrenaline-evoked contractions were greater in cav-1KO than WT arteries. (-)-Isoprenaline relaxed WT arteries (-log EC50M=7.3) more potently than cav-1KO arteries (-log EC50M=6.8); the effects were antagonized partially and similarly by the beta2-selective antagonist ICI118551 (50 nM). The (-)-isoprenaline-evoked relaxation was partially antagonized by the beta1-adrenoceptor-selective antagonist CGP20712 (300 nM) in WT but not cav-1KO arteries. The beta3-adrenoceptor-selective antagonist L748337 (100 nM) partially antagonized the relaxant effects of (-)-isoprenaline in cav-1KO but not in WT arteries. BRL37344 partially relaxed arteries through beta3-adrenoceptors in cav-1KO but not WT. The relaxant effects of BRL37344 were decreased by the NO synthase inhibitor OmegaL-nitroarginine.


CONCLUSIONS
The function of arterial alpha1- and beta2-adrenoceptors is similar in cav-1KO and WT mice. beta1-adrenoceptor-mediated relaxation in WT is lost in cav-1KO and replaced by the appearance of beta3-adrenoceptors.
Neidhold
S
S
Department of Pharmacology, Technical University of Dresden, Dresden, Germany.
Eichhorn
B
B
Kasper
M
M
Ravens
U
U
Kaumann
A J
AJ
D000818:Animals; D001158:Arteries; D051242:Caveolin 1 / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D006614:Hindlimb / Q000098:blood supply; D051379:Mice; D018345:Mice, Knockout / Q000502:physiology*; D008854:Microscopy, Electron; D016133:Polymerase Chain Reaction; D011942:Receptors, Adrenergic, alpha / Q000235:genetics / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000502:physiology*
D051242:Caveolin 1; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta