Involvement of neutral sphingomyelinase in the angiotensin II signaling pathway

2015 ◽  
Vol 308 (10) ◽  
pp. F1178-F1187 ◽  
Author(s):  
Rocio Bautista-Pérez ◽  
Leonardo del Valle-Mondragón ◽  
Agustina Cano-Martínez ◽  
Oscar Pérez-Méndez ◽  
Bruno Escalante ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Angiotensin Ii ◽  
Rat Kidney ◽  
Muscle Layer ◽  
Ang Ii ◽  
Renal Vasculature ◽  
Isolated Perfused Rat Kidney ◽  
Renal Vasoconstriction ◽  
Neutral Sphingomyelinase ◽  
Perfused Rat Kidney

The possibility that angiotensin II (ANG II) exerts its effects through the activation of neutral sphingomyelinase (nSMase) has not been tested in kidneys. The results of the present study provide evidence for the activity and expression of nSMase in rat kidneys. In isolated perfused rat kidney, ANG II-induced renal vasoconstriction was inhibited by GW4869, an inhibitor of nSMase. We used nSMase for investigating the signal transduction downstream of ceramide. nSMase constricted the renal vasculature. An inhibitor of ceramidase (CDase), N-oleoylethanolamine (OEA), enhanced either ANG II- or nSMase-induced renal vasoconstriction. To demonstrate the interaction between the nSMase and cytosolic phospholipase A2 (cPLA2) signal transduction pathways, we evaluated the response to nSMase in the presence and absence of inhibitors of arachidonic acid (AA) metabolism: arachidonyl trifluoromethyl ketone (AACOCF3), an inhibitor of cPLA2; 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of all AA pathways; indomethacin, an inhibitor of cyclooxygenase (COX); furegrelate, a thromboxane A2 (TxA2)-synthase inhibitor; and SQ29548 , a TxA2-receptor antagonist. In these experiments, the nSMase-induced renal vasoconstriction decreased. ANG II or nSMase was associated with an increase in the release of thromboxane B2 (TxB2) in the renal perfusate of isolated perfused rat kidney. In addition, the coexpression of the ceramide with cPLA2, was found in the smooth muscle layer of intrarenal vessels. Our results suggest that ANG II stimulates ceramide formation via the activation of nSMase; thus ceramide may indirectly regulate vasoactive processes that modulate the activity of cPLA2 and the release of TxA2.

Bidirectional regulation of renal hemodynamics by activation of PAR1 and PAR2 in isolated perfused rat kidney

2003 ◽  
Vol 285 (1) ◽  
pp. F95-F104 ◽  
Author(s):  
Yu Gui ◽  
Rodger Loutzenhiser ◽  
Morley D. Hollenberg
Keyword(s):  
Rat Kidney ◽  
Renal Perfusion ◽  
Renal Hemodynamics ◽  
Ang Ii ◽  
Isolated Perfused Rat Kidney ◽  
Renal Vasoconstriction ◽  
Bidirectional Regulation ◽  
Perfused Rat Kidney ◽  
Proteinase Activated Receptors ◽  
The Impact

Proteinase-activated receptors (PARs) are activated by either serine proteinases or synthetic peptides corresponding to the NH2-terminal tethered ligand sequences that are unmasked by proteolytic cleavage. Although PARs are highly expressed in the kidney, their roles in regulating renal function are not known. In the present study, we evaluated the impact of PAR activation on renal hemodynamics using PAR1- and PAR2-activating peptides (TFLLR-NH2 and SLIGRL-NH2) and proteinases (thrombin and trypsin) as PAR agonists in the isolated perfused rat kidney preparation. PAR1 activation resulted in renal vasoconstriction and a marked reduction in the glomerular filtration rate (GFR). In contrast, PAR2 activation caused vasodilation, partially reversing the vasoconstriction induced by TFLLR-NH2 and ANG II and increasing GFR that had been prereduced by ANG II. The vasoconstrictor actions of PAR1 activation were abolished by protein kinase C inhibition. The PAR2-induced vasodilation was only partially blocked by NG-nitro-l-arginine methyl ester, suggesting both nitric oxide-dependent and -independent mechanisms. Although PAR4 mRNA was detected in renal parenchyma, the PAR4-activating peptide AYPGKF-NH2 had no effect on renal perfusion flow rate. We conclude that PAR1 and PAR2 play bidirectional roles in the regulation of renal hemodynamics.

Interactions of cAMP-mediated vasodilators with angiotensin II in rat kidney during hypertension

1993 ◽  
Vol 265 (6) ◽  
pp. F845-F852 ◽  
Author(s):  
C. Chatziantoniou ◽  
X. Ruan ◽  
W. J. Arendshorst
Keyword(s):  
Angiotensin Ii ◽  
G Protein ◽  
Rat Kidney ◽  
Control Period ◽  
Ang Ii ◽  
Dibutyryl Camp ◽  
Renal Vasculature ◽  
Spontaneously Hypertensive ◽  
Electromagnetic Flowmetry ◽  
Wistar Kyoto

In previous studies [C. Chatziantoniou and W.J. Arendshorst. Am. J. Physiol. 263 (Renal Fluid Electrolyte Physiol. 32): F573-F580, 1992], we reported that vasodilator prostaglandins (PGs) are defective in buffering the angiotensin II (ANG II)-induced vasoconstriction in the renal vasculature of spontaneously hypertensive rats (SHR). The purpose of the present study was to determine whether this defect in SHR kidneys is specific to PGs or generalized to the action of vasodilators and to gain insight into which intracellular signal(s) mediates this abnormality. Renal blood flow (RBF; electromagnetic flowmetry) was measured in 7 wk-old anesthetized, euvolemic SHR and normotensive Wistar-Kyoto (WKY) rats pretreated with indomethacin to avoid interactions with endogenous PGs. ANG II (2 ng) was injected into the renal artery before and during continuous intrarenal infusion of fenoldopam [DA1 receptor agonist and G protein-dependent stimulator of adenosine 3',5'-cyclic monophosphate (cAMP)], forskolin (G protein-independent stimulator of cAMP), dibutyryl-cAMP (soluble cAMP), and acetylcholine (cGMP stimulator). Each vasodilator was infused at a low dose that did not affect baseline arterial pressure or RBF. In the control period, ANG II reduced RBF by 50% in both strains. Infusion of fenoldopam significantly blunted the ANG II-induced vasoconstriction in WKY, but not in SHR. In contrast, forskolin, dibutyryl-cAMP, and acetylcholine effectively buffered the vasoconstriction due to ANG II in both SHR and WKY. These results suggest that renal vasodilators acting through receptor binding to stimulate the cAMP signaling pathway are ineffective in counteracting the ANG II-induced vasoconstriction in SHR kidneys. (ABSTRACT TRUNCATED AT 250 WORDS)

Effects of chloride channel blockers on rat renal vascular responses to angiotensin II and norepinephrine

2004 ◽  
Vol 286 (2) ◽  
pp. F323-F330 ◽  
Author(s):  
Joen Steendahl ◽  
Niels-Henrik Holstein-Rathlou ◽  
Charlotte Mehlin Sorensen ◽  
Max Salomonsson
Keyword(s):  
Angiotensin Ii ◽  
Niflumic Acid ◽  
Channel Blockers ◽  
Ang Ii ◽  
Renal Vasculature ◽  
Renal Vasoconstriction ◽  
Electromagnetic Flowmetry ◽  
Control Response ◽  
Renal Vascular

The aim of the present study was to investigate the role of Ca2+-activated Cl- channels in the renal vasoconstriction elicited by angiotensin II (ANG II) and norepinephrine (NE). Renal blood flow (RBF) was measured in vivo using electromagnetic flowmetry. Ratiometric photometry of fura 2 fluorescence was used to estimate intracellular free Ca2+ concentration ([Ca2+]i) in isolated preglomerular vessels from rat kidneys. Renal arterial injection of ANG II (2-4 ng) and NE (20-40 ng) produced a transient decrease in RBF. Administration of ANG II (10-7 M) and NE (5 × 10-6 M) to the isolated preglomerular vessels caused a prompt increase in [Ca2+]i. Renal preinfusion of DIDS (0.6 and 1.25 μmol/min) attenuated the ANG II-induced vasoconstriction to ∼35% of the control response, whereas the effects of NE were unaltered. Niflumic acid (0.14 and 0.28 μmol/min) and 2-[(2-cyclopentenyl-6,7-dichloro-2,3-dihydro-2-methyl-1-oxo-1 H-inden-5-yl)oxy]acetic acid (IAA-94; 0.045 and 0.09 μmol/min) did not affect the vasoconstrictive responses of these compounds. Pretreatment with niflumic acid (50 μM) or IAA-94 (30 μM) for 2 min decreased baseline [Ca2+]i but did not change the magnitude of the [Ca2+]i response to ANG II and NE in the isolated vessels. The present results do not support the hypothesis that Ca2+-activated Cl- channels play a crucial role in the hemodynamic effects of ANG II and NE in rat renal vasculature.

Nitric oxide modulates angiotensin II- and norepinephrine-dependent vasoconstriction in rat kidney

1996 ◽  
Vol 270 (3) ◽  
pp. R630-R635 ◽  
Author(s):  
N. Parekh ◽  
L. Dobrowolski ◽  
A. P. Zou ◽  
M. Steinhausen
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Angiotensin Ii ◽  
Rat Kidney ◽  
Ang Ii ◽  
No Donor ◽  
Renal Vasoconstriction ◽  
Medullary Blood Flow ◽  
Series Of Experiments ◽  
Synthase Inhibitor

This study compared the vasoconstrictor action of angiotensin II (ANG II) and norepinephrine (NE) with different levels of nitric oxide (NO) in the kidney of anesthetized rats. In one series of experiments, the drugs were infused intravenously, and systemic NO content was reduced by a NO synthase inhibitor, nitro-L-arginine methyl ester (L-NAME). L-NAME significantly enhanced the renal blood flow (RBF) reduction produced by ANG II from 26 to 49%, but it had no significant effect on the change in RBF induced by NE. Medullary blood flow was not influenced by either ANG II or NE given alone or given after L-NAME. In the second series of experiments, all drugs were infused into the renal artery to avoid their systemic and, hence, extrarenal effects. In these experiments, renal content of NO was increased by the NO donor sodium nitroprusside (SNP), decreased by L-NAME, or restored by replacing endogenous NO by exogenous NO (L-NAME + SNP). Effects of both ANG II and NE on RBF were similarly and significantly attenuated by SNP (60% of control), enhanced by L-NAME (200% of control), and restored by L-NAME + SNP (90% of control, not significant). Our results indicate that NO attenuates the renal vasoconstriction due to ANG II or NE and that the antagonism between vasoconstrictors and NO is not due to a constrictor-induced production of NO because exogenous and endogenous NO were equally effective.

The Effect of Angiotensin upon the Vasculature of the Isolated Perfused Rat Kidney

1974 ◽  
Vol 46 (5) ◽  
pp. 647-650
Author(s):  
R. B. Cross ◽  
J. W. Trace ◽  
J. R. Vattuone
Keyword(s):  
Angiotensin Ii ◽  
Perfusion Pressure ◽  
Rat Kidney ◽  
Total Flow ◽  
Renal Vasculature ◽  
Low Concentrations ◽  
Perfused Rat Kidney ◽  
Renal Flow ◽  
Intrarenal Distribution ◽  
Isolated Rat

1. The effect of angiotensin II-amide upon the intrarenal distribution of perfusate was studied in the isolated rat kidney. 2. Low concentrations of angiotensin, 4·86 pmol/l (0·005 μg/l), reduced the flow rate through the papilla but did not alter total flow. 3. Higher concentrations of angiotensin, 0·486 nmol/l (0·5 μg/l), reduced total renal flow but did not decrease papillary perfusion. 4. In these experiments the perfusion pressure was maintained constant, indicating that the changes in flow were due to a direct effect of angiotensin upon the renal vasculature.

scholarly journals Role of protein kinase C in renal vasoconstriction caused by angiotensin II

1990 ◽  
Vol 259 (3) ◽  
pp. C421-C426 ◽  
Author(s):  
H. Scholz ◽  
A. Kurtz
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Rat Kidney ◽  
Channel Blockers ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Protein Kinase C Inhibitors ◽  
Kinase C ◽  
Renal Vascular

In this study we have examined the subcellar pathways along which angiotensin II (ANG II) causes renal vasoconstriction. Using the isolated perfused rat kidney model, we found that renal vasoconstriction produced by ANG II (100 pM) was not altered by the calmodulin antagonists calmidazolium (1 microM) and N-(6-aminohexyl)-5-chloro-1-naphthalensulfonamide (W-7, 10 microM) but was blunted by staurosporine (100 nM) and 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7, 50 microM), two structurally distinct putative protein kinase C inhibitors. The phorbol ester 4 alpha-phorbol 12,13-didecanoate (1-100 nM) did not alter renal vascular resistance, whereas phorbol 12-myristate 13-acetate (PMA, 1-100 nM) caused potent and dose-dependent vasoconstriction that was prevented by staurosporine (100 nM) and H-7 (50 microM). The vasoconstrictory effects of ANG II and PMA were attenuated by the calcium channel blockers verapamil (5 microM) and nifedipine (5 microM) and were reversibly inhibited when cobaltous chloride (2 mM) was added to the perfusate. Taken together, our findings support the concept that the renal vasoconstrictory effect of ANG II is essentially mediated by protein kinase C activation, which either requires or enhances the entrance of extracellular calcium.

DuP 753 Is a Potent Nonpeptide Antagonist of Angiotensin II Receptors in Isolated Perfused Rat Kidney and Cultured Renal Cells

1991 ◽  
Vol 4 (4_Pt_2) ◽  
pp. 303S-308S ◽  
Author(s):  
Beatriz M.A. Fontoura ◽  
Daniel R. Nussenzveig ◽  
Pieter B.M.W.M. Timmermans ◽  
Thomas Maack
Keyword(s):  
Angiotensin Ii ◽  
Rat Kidney ◽  
Angiotensin Ii Receptors ◽  
Renal Cells ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney

Blockade of Renin Release by Lanthanum

1974 ◽  
Vol 48 (s2) ◽  
pp. 31s-32s
Author(s):  
A. G. Logan ◽  
I. Tenyi ◽  
T. Quesada ◽  
W. S. Peart ◽  
A. S. Breathnach ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Renin Secretion ◽  
Renin Release ◽  
Isolated Perfused Rat Kidney ◽  
Renal Vasoconstriction ◽  
Perfused Rat Kidney ◽  
Stimulation Of

1. The effects of lanthanum on renin release and renal vasoconstriction were studied in the isolated perfused rat kidney. 2. Lanthanum reduced noradrenaline-induced renal vasoconstriction. 3. Lanthanum prevented isoprenaline-induced and glucagon-induced stimulation of renin secretion.

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