Calcium retention and increased vascular reactivity caused by a hypothalamic sodium transport inhibitor.
1. Using a previously established method of isolating an active-sodium-transport inhibitor (ASTI) from hypothalamic cell culture medium, the inhibitor was isolated and partially purified from sequential passages through Sephadex G-25 and h.p.l.c., and its effects on de-endothelialized rabbit aortic strips were investigated. 2. ASTI caused a cumulative concentration-dependent increase in tension which reversed slowly after wash, and the wash showed an identical effect on fresh strips. 3. Ouabain, used as a control, also caused a concentration-dependent increase in tension which reached a plateau at a concentration of 10 mmol/l. Both ouabain and ASTI caused a significant potentiation of the vasoconstrictor effect of noradrenaline at concentrations of 1 nmol/l-0.1 mmol/l. 4. Both ASTI and ouabain caused a significantly greater (P less than 0.01) calcium retention than control medium in aortic strips. 5. Incubation of ASTI with prolidase, chymotrypsin and carboxypeptidase A destroyed the vasoconstrictor effects as well as its inhibitory effects on sodium, potassium-dependent adenosine triphosphatase and sodium efflux from erythrocytes, but leucine aminopeptidase was ineffective. 6. These studies suggest that hypothalamic cells in culture release a peptidic inhibitor of active sodium transport which increases vascular reactivity, potentiates vasoconstrictor effects of noradrenaline and causes calcium retention.
Mir
M A
MA
Department of Medicine, University of Wales College of Medicine, Cardiff, U.K.
Morgan
K
K
Chappell
S
S
Lewis
M
M
Spurlock
G
G
Collins
P
P
Collins
P
P
Lewis
M
M
Scanlon
M
M
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007031:Hypothalamus / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D012964:Sodium / Q000037:antagonists & inhibitors*
D010455:Peptides; C029311:serum sodium transport inhibitor; D012964:Sodium; D002118:Calcium; D009638:Norepinephrine