title: The mechanism of relaxation induced by atrial natriuretic peptide in the porcine renal artery.
abstract: 1. The mechanisms underlying the relaxation of the porcine renal artery induced by atrial natriuretic peptide (ANP) were investigated, using front-surface fluorimetry with fura-2 and receptor-coupled permeabilization by alpha-toxin. 2. ANP decreased the cytosolic Ca2+ concentration ([Ca2+]i) and tension during the contraction induced by a high external K+ solution, in a concentration-dependent manner. This ANP-induced decrease in [Ca2+]i during the contraction induced by high K+ solution was composed of two phases, an initial rapid phase, followed by a maintenance phase. The initial rapid decrease in [Ca2+]i, but not the maintained decrease in [Ca2+]i, was inhibited when the tissue was treated with thapsigargin, a selective Ca2+ pump inhibitor of the sarcoplasmic reticulum. When the tissues were treated with thapsigargin and external Ca2+ was replaced by Ba2+, which cannot be transported by the Ca2+ pump, ANP did not induce a decrease in [Ba2+]i, even though the elevation of tension induced by Ba2+ was strongly inhibited. 3. In the absence of extracellular Ca2+, ANP inhibited the release of Ca2+ from the intracellular store induced by noradrenaline (NA). 4. The [Ca2+]i (abscissa scale)-tension (ordinate scale) relationship observed during the contraction induced by various concentrations of high external K+ solution was shifted downwards by the addition of 10(-8) M ANP, indicating that, at any given [Ca2+]i, the tension generated by high K+ solution was considerably inhibited by the addition of 10(-8) M ANP. The [Ca2+]i-tension curve of the contraction obtained by the cumulative application of external Ca2+ (0-3.75 mM) during depolarization with 118 mM K+ solution was shifted to the left by 3 x 10(-7) M NA. This NA-induced [Ca2+]i-tension relationship was shifted to the right by 10(-8) M ANP, indicating that the ANP-induced reduction of Ca(2+)-sensitivity operates during the contraction induced by NA. 5. In alpha-toxin-permeabilized preparations, ANP induced relaxation of tissues precontracted with a mixture of 3 x 10(-7) M Ca2+, 10(-5) M guanosine 5'-triphosphate (GTP) and 10(-6) M NA. Thus a component of ANP-induced relaxation took place by way of a reduction in the Ca2+ sensitivity of the myofilaments, independent of changes in [Ca2+]i. 6. These results indicate that ANP induces relaxation of the porcine renal artery by: (1) reducing [Ca2+]i mainly via the activation of the Ca2+ pumps located on the sarcoplasmic reticulum and sarcolemma, as well as via inhibition of agoinist-induced release of Ca2+ from the intracellular store; and (2) decreasing the Ca(2+)-sensitivity of the contractile elements.
authors: Division of Molecular Cardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors: H
authors: H
authors: Seguchi
authors: J
authors: J
authors: Nishimura
authors: K
authors: K
authors: Toyofuku
authors: S
authors: S
authors: Kobayashi
authors: J
authors: J
authors: Kumazawa
authors: H
authors: H
authors: Kanaide
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D011188:Potassium / Q000737:chemistry; D012077:Renal Artery / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D012996:Solutions; D013552:Swine; D010738:Type C Phospholipases / Q000494:pharmacology
chemical_list: D012996:Solutions; D009320:Atrial Natriuretic Factor; D010738:Type C Phospholipases; D011188:Potassium; D002118:Calcium