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Role of Protein Kinase C in contraction of human and rat pulmonary arteries
J Mol
Cell
Cardiol
23 (Supplement
IV)
(1991)
160 PLATELET SODIUM-PROTON EXCHANGER RATES IN YOUNG ADULTS WITH CHILDHOOD HYPERTENSION HISTORY. J P SALLE& P BARTHE, F BEGASSE, F BOUISSOU, H CHAP, E! CHAMONTIN. INSERM Unit 326 and Young $$lt&EEod Pressure Study Group, Hopltal Purpan 31059TOULOUSE cedex In order to assess the relation betweenincreasedcellular sodium-proton(Na+/H+) exchangeand cardiovascularabnormalitiesin essentialhypertension(EH), 20youn sub’ectsaspart of an ongoing longitudinal study weretestedfor the platelets Na+/ I-F exehangeusingthe amiloride sensitivesodiumdependentcomponentof platelet volume changeunder cytoplasmic acidification induced by a sodiumpropionate medium; cell volumesweredeterminedby electronic cell sizing(Livne et al, Lancer, 1987;i: 533b).Data of ambulatory blood pressurerecording (ABPR) defined3 grou s accordin to the presenceof normotension(I, n=lO), or of established(II. n=2) or of gorderline (f II, n=9) hqertension. Hypertensive subjects( roups II and III) had increasedvaluesof Na /H exchange(k coefficent. mean(SEa, ): 0.295 and 0.299 (O.O6),resectivelyvs 0.228(0.05) in normotensives.Na+/H+ rateswere significantly related to lgBPR data (ti.9, p
161
PUTHYROID HORMONE (PTH) AND PARATHYROID HORMONE-RELATED PROTEIN (PTH~P) STIMULATE RENIN RELEASE FROM ISOLATED PERFUSED RAT KIDNEY (IPK): A CALCIUM-DEPENDENT EFFECT. C. Saussine, M.J. Muss0 and J.J. Helwlg. Labo Physio. RQnale, Hospices Civils, Universite Louis Pasteur, Strasbourg, France. Rat PTH-(l-34) and human PTHrP-(1-34) vasodilate the rat IPK, stimulate CAMP in preglomerular arterioles and possess common receptors on these vessels. Since both cellular Ca decrease and CAMP increase have been shown to trigger renin release rate @RR), these results prompted us to explore the effect of PTH and PTHrP on the RRR Non-filtering IPK were used from rat IPK perfused with constant pressures and flows. to avoid the influence of distal sodium load and peptide degradation. Renin activities which accumulated in the closed perfusion circuit were measured by their capacity to convert angiotensinogen into angio I. The comparison of control with PTHtreated (100 nM) IPK showed that in 1 mM Ca2+ perfusate the RRR was increased to 148I In 0 mM Ca2+ this response was suppressed while in 2 mM Ca2+ the RRR in response to PTH increased to 190X over control. With verapamil (0.1 mM) in the perfusate, which stimulated the basal RRR, PTH was unable to further stimulate the RRR. But, PTH strongly reversed the inhibiting effect of 20 nM BAY-K8644 on basal RRR. Similar results were obtained with 100 nM PTHrP. Our data suggest that PTH and PTHrP are able to increase RRR by a mechanism independent from baroreceptors and macula densa but involving the inhibition of Ca inflows into the secreting cells.
162
ROLE OF PROTEIN KINASE C IN CONTRACl’ION OF HUMAN AND RAT PULMONARY ARTERIES. J.P. Savlneau, R. Ma&an, H. Cnvel. Laboratoire de Physiologie, Universite de Bordeaux II, 33076 Bordeaux - France.
ProteinKinaseC (PKC)mayplay amajorregulatoryrolein themechanical activity of vascular
smooth muscles. In the present work, we studied the effects of phorbol 12, 13 dibutyrate (PDB), a PKC activator, on the tension of human and rat pulmonary arteries. Expetiments were performed on strips isolated from the pulmonary artery of rat (RPA) and human (HPA) dissected from lungs obtained at dmracotomy. PDB (2 to 50 nM) and (50 nM to 1 @I) induced sustained and
concentration-dependent concentration themaximalamplitudeof whichwas182+ 1596(n = 5) and
205 + 18 % (n = 6) of that induced by the potassium-rich (80 mM K+) solutiorin HPA and RAP, respectively. Both in HPA and RAP, PDB-induced concentration was partially modified by the removal of external calcium ions or by addition of verapamil(l0 PM) (15 f 7 46, n = 4, reduction of the maximal response). In RAP trifluoroperazine (10 PM) a calmodulin antagonist had no effect on PDB contractions (5 bundles). In contrast, i-17 (si, p&f) and phloretin (lo @I) PKC inhibitors reduced the maximal PDB contraction by 45 + 10 96 (n = 3) and 65 + 15 % (n = 4). respectively. Both in I-WA and RAP, the inactive ph&oll3,2O dketate (10 nM to 1 @I) had no effect. This study shows that PDB is a potent vasoconstrictor in pulmonaty vessels. Its action mainly depends on PKC which seems to be @ortant in controlling tone in these arterles. S.54
Cell
Cardiol
23 (Supplement
IV)
(1991)
160 PLATELET SODIUM-PROTON EXCHANGER RATES IN YOUNG ADULTS WITH CHILDHOOD HYPERTENSION HISTORY. J P SALLE& P BARTHE, F BEGASSE, F BOUISSOU, H CHAP, E! CHAMONTIN. INSERM Unit 326 and Young $$lt&EEod Pressure Study Group, Hopltal Purpan 31059TOULOUSE cedex In order to assess the relation betweenincreasedcellular sodium-proton(Na+/H+) exchangeand cardiovascularabnormalitiesin essentialhypertension(EH), 20youn sub’ectsaspart of an ongoing longitudinal study weretestedfor the platelets Na+/ I-F exehangeusingthe amiloride sensitivesodiumdependentcomponentof platelet volume changeunder cytoplasmic acidification induced by a sodiumpropionate medium; cell volumesweredeterminedby electronic cell sizing(Livne et al, Lancer, 1987;i: 533b).Data of ambulatory blood pressurerecording (ABPR) defined3 grou s accordin to the presenceof normotension(I, n=lO), or of established(II. n=2) or of gorderline (f II, n=9) hqertension. Hypertensive subjects( roups II and III) had increasedvaluesof Na /H exchange(k coefficent. mean(SEa, ): 0.295 and 0.299 (O.O6),resectivelyvs 0.228(0.05) in normotensives.Na+/H+ rateswere significantly related to lgBPR data (ti.9, p
161
PUTHYROID HORMONE (PTH) AND PARATHYROID HORMONE-RELATED PROTEIN (PTH~P) STIMULATE RENIN RELEASE FROM ISOLATED PERFUSED RAT KIDNEY (IPK): A CALCIUM-DEPENDENT EFFECT. C. Saussine, M.J. Muss0 and J.J. Helwlg. Labo Physio. RQnale, Hospices Civils, Universite Louis Pasteur, Strasbourg, France. Rat PTH-(l-34) and human PTHrP-(1-34) vasodilate the rat IPK, stimulate CAMP in preglomerular arterioles and possess common receptors on these vessels. Since both cellular Ca decrease and CAMP increase have been shown to trigger renin release rate @RR), these results prompted us to explore the effect of PTH and PTHrP on the RRR Non-filtering IPK were used from rat IPK perfused with constant pressures and flows. to avoid the influence of distal sodium load and peptide degradation. Renin activities which accumulated in the closed perfusion circuit were measured by their capacity to convert angiotensinogen into angio I. The comparison of control with PTHtreated (100 nM) IPK showed that in 1 mM Ca2+ perfusate the RRR was increased to 148I In 0 mM Ca2+ this response was suppressed while in 2 mM Ca2+ the RRR in response to PTH increased to 190X over control. With verapamil (0.1 mM) in the perfusate, which stimulated the basal RRR, PTH was unable to further stimulate the RRR. But, PTH strongly reversed the inhibiting effect of 20 nM BAY-K8644 on basal RRR. Similar results were obtained with 100 nM PTHrP. Our data suggest that PTH and PTHrP are able to increase RRR by a mechanism independent from baroreceptors and macula densa but involving the inhibition of Ca inflows into the secreting cells.
162
ROLE OF PROTEIN KINASE C IN CONTRACl’ION OF HUMAN AND RAT PULMONARY ARTERIES. J.P. Savlneau, R. Ma&an, H. Cnvel. Laboratoire de Physiologie, Universite de Bordeaux II, 33076 Bordeaux - France.
ProteinKinaseC (PKC)mayplay amajorregulatoryrolein themechanical activity of vascular
smooth muscles. In the present work, we studied the effects of phorbol 12, 13 dibutyrate (PDB), a PKC activator, on the tension of human and rat pulmonary arteries. Expetiments were performed on strips isolated from the pulmonary artery of rat (RPA) and human (HPA) dissected from lungs obtained at dmracotomy. PDB (2 to 50 nM) and (50 nM to 1 @I) induced sustained and
concentration-dependent concentration themaximalamplitudeof whichwas182+ 1596(n = 5) and
205 + 18 % (n = 6) of that induced by the potassium-rich (80 mM K+) solutiorin HPA and RAP, respectively. Both in HPA and RAP, PDB-induced concentration was partially modified by the removal of external calcium ions or by addition of verapamil(l0 PM) (15 f 7 46, n = 4, reduction of the maximal response). In RAP trifluoroperazine (10 PM) a calmodulin antagonist had no effect on PDB contractions (5 bundles). In contrast, i-17 (si, p&f) and phloretin (lo @I) PKC inhibitors reduced the maximal PDB contraction by 45 + 10 96 (n = 3) and 65 + 15 % (n = 4). respectively. Both in I-WA and RAP, the inactive ph&oll3,2O dketate (10 nM to 1 @I) had no effect. This study shows that PDB is a potent vasoconstrictor in pulmonaty vessels. Its action mainly depends on PKC which seems to be @ortant in controlling tone in these arterles. S.54