Parathyroid hormone acute vascular effect is mediated by decreased Ca2+ uptake and enhanced cAMP level.
Cardiovascular effects of parathyroid hormone (PTH) have been recently described. Pharmacological doses of PTH both reduce arterial pressure and increase blood flow of vascular beds. Two possible cellular mechanisms were investigated: (a) transmembrane Ca2+ fluxes and (b) cyclic AMP response in vascular smooth muscle. In vivo, results in the rat show that injection of synthetic bovine 1-34 fragment of PTH (bPTH-(1-34] produced a rapid (1-2 min) but transient (5-16 min) hypotensive effect which was dose-related (0.4-4 nmol.kg-1). In the in vitro studies on isolated rat aorta, bPTH-(1-34) partially inhibited noradrenaline (NA)-induced contractions by decreasing the sustained tonic component dependent on extracellular Ca2+. bPTH-(1-34) also produced relaxation of aorta preconstricted with NA or prostaglandin F2 alpha. Measurements of the lanthanum-resistant Ca2+ pool using 45Ca2+ showed that bPTH-(1-34) decreased basal Ca2+ uptake and partially inhibited Ca2+ uptake stimulated by NA or K+-depolarizing solution in a concentration-dependent fashion. In addition, bPTH-(1-34) caused a concentration-related increase in cyclic AMP in rat isolated aortic tissues. Hypotensive and vasorelaxing effects of bPTH-(1-34) thus appear to be mediated by a decrease in the amount of Ca2+ available for contraction and by an increase in cyclic AMP response in vascular smooth muscle cells.
Schleiffer
R
R
Laboratoire de Pharmacologie Cellulaire et Moléculaire, CNRS UA 600, Faculté de Pharmacie, Université Louis Pasteur, Illkirch, France.
Bergmann
C
C
Pernot
F
F
Gairard
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000493:pharmacokinetics*; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D010281:Parathyroid Hormone; D010446:Peptide Fragments; C025076:parathyroid hormone (1-34), bovine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium; D009638:Norepinephrine