Na+-K+ pump and Na+-K+ co-transport in cultured vascular smooth muscle cells from spontaneously hypertensive and normotensive rats

Orlov, S.N.; Resink, Thérèse J.; Bernhardt, J.; Bühler, Fritz R.

doi:10.1097/00004872-199208000-00006

Cited by 29 publications

(14 citation statements)

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“…On the other hand, other researchers detected augmented NKCC in VSMR from rodents with secondary hypertension [15,24] and enhanced content of endogenous NKCC inhibitor in the plasma of salt-sensitive rats [5], suggesting that the carrier is subjected to cell-typespecific regulation by diverse stimuli. Indeed, no systematic involvement of Ca 2+ , cAMP and cGMP has been detected in studies of NKCC in human and rat erythrocytes [17], whereas in VSMR and cultured VSMC, this carrier was activated by Ca 2+ i -raising vasoconstrictors, including angiotensin II, and was inhibited by cAMP-and cGMP-mediated vasodilators [3,4,42,49,55,57]. Opposing regulation by vasodilators was documented in a study of Na + -independent K + ,Cl − cotransport (KCC) [2], i.e.…”

Section: Introductionmentioning

confidence: 99%

Cell-volume-dependent vascular smooth muscle contraction: role of Na+, K+, 2Cl? cotransport, intracellular Cl? and L-type Ca2+ channels

Anfinogenova

Baskakov

Ковалев

et al. 2004

Pflugers Arch - Eur J Physiol

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This study elucidates the role of cell volume in contractions of endothelium-denuded vascular smooth muscle rings (VSMR) from the rat aorta. We observed that hyposmotic swelling as well as hyper- and isosmotic shrinkage led to VSMR contractions. Swelling-induced contractions were accompanied by activation of Ca2+ influx and were abolished by nifedipine and verapamil. In contrast, contractions of shrunken cells were insensitive to the presence of L-type channel inhibitors and occurred in the absence of Ca2+ o. Thirty minutes preincubation with bumetanide, a potent Na+, K+, CI- cotransport (NKCC) inhibitor, decreased Cl(-)i content, nifedipine-sensitive 45Ca uptake and contractions triggered by modest depolarization ([K+]o = 36 mM). Elevation of [K+]o to 66 mM completely abolished the effect of bumetanide on these parameters. Bumetanide almost completely abrogated phenylephrine-induced contraction, partially suppressed contractions triggered by hyperosmotic shrinkage, but potentiated contractions of isosmotically shrunken VSMR. Our results suggest that bumetanide suppresses contraction of modestly depolarized cells via NKCC inhibition and Cl(-)i-mediated membrane hyperpolarization, whereas augmented contraction of isosmotically shrunken VSMR by bumetanide is a consequence of suppression of NKCC-mediated regulatory volume increase. The mechanism of bumetanide inhibition of contraction of phenylephrine-treated and hyperosmotically shrunken VSMR should be examined further.

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Section: Introductionmentioning

confidence: 99%

Cell-volume-dependent vascular smooth muscle contraction: role of Na+, K+, 2Cl? cotransport, intracellular Cl? and L-type Ca2+ channels

Anfinogenova

Baskakov

Ковалев

et al. 2004

Pflugers Arch - Eur J Physiol

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“…Na+/H+ exchange activity in confluent, quiescent cultures of VSMC (in 12-well plates) was determined as described previously [24]. The incubation solution for 22Na uptake contained 60 mM NaCl.…”

Section: Measurement Ofna+/if* Exchangementioning

confidence: 99%

“…2-3 pCi 22NaCl/ml. and either without or with inclusion of 10 p.M EIPA (to inhibit Na+/H4 exchange activity) [24], Cells were incubated for 3 min both in the absence (basal) and presence of lipoproteins. Na+/H+ exchange activ ity is represented by EIPA-sensitive-(ouabain and bumetanide)-insensitive 22Na influx [24].…”

Section: Measurement Ofna+/if* Exchangementioning

confidence: 99%

Cellular Signalling by Lipoproteins in Cultured Smooth Muscle Cells from Spontaneously Hypertensive Rats

Resink

Rybin²,

Bernhardt³

et al. 1993

J Vasc Res

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We investigated pivotal signalling responses of cultured aortic smooth muscle cells (VSMC) from the spontaneously hypertensive rat (SHR) and the normotensive Wistar Kyoto rat (WKY) to lipoproteins. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL₃) stimulated a time- and dose-dependent accumulation of inositol phosphates in VSMC. SHR and WKY VSMC exhibited comparable half-maximal dose requirements (≈13 µg/ml for LDL and ≈14 µg/ml for HDL₃), although, at any given dose, the response of SHR VSMC was significantly greater than WKY VSMC. Simultaneous addition of LDL and HDL₃ to VSMC resulted in additive stimulatory effects on phosphoinositide catabolism. Pertussis toxin pretreatment of VSMC completely negated the stimulatory effects of LDL and HDL₃ on IP accumulation. [³²P]-ADP ribosylation and immunoblotting studies revealed the guanine nucleotide-binding (G protein) substrate(s) for pertussis toxin to be a G_i protein(s). SHR and WKY VSMC did not differ with respect to levels of G_iα or G_β, and, thus, the amplified responsiveness in SHR VSMC cannot be attributed to alterations in levels of pertussis toxin-sensitive G protein. The spectrum of signalling responses elicited by LDL and HDL₃ are similar to those elicited by vasoactive hormones, and thus lipoproteins may, via stimulation of phosphoinositide catabolism, ⁴⁵Ca²⁺ uptake and Na⁺/H⁺-exchange, directly regulate smooth muscle cell growth and contraction.

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“…Another pos sibility might be a direct action within the heart. Although there is no direct evidence that a loop diuretic would possess any beneficial biochemical effect in connec tion with cardiac cells, the possible involvement of the Na+, K+, 2Cl--cotransport system during the develop ment of hypertension and vascular hypertrophy has been suggested (29,30). Therefore, it is assumed that the Na+, K+, 2C1--cotransport system, which may be inhibitable with M17055 as well as the other loop diuretics, would be involved in the development of cardiovascular hyper trophy.…”

Section: Laboratory Measurementsmentioning

confidence: 99%

“…As for the mecha nism of developing and sustaining the vascular hyper trophy, the tissue renin-angiotensin system has been indi cated to be involved (23,26). On the other hand, the invol vement of the Na+, K+, 2C1--cotransport system (29,30) or Na+/H+ exchanger (34) should be considered, being similar to the case with cardiac hypertrophy. However, the mechanism for the vascular action of M17055 remains to be elucidated.…”

Section: Laboratory Measurementsmentioning

confidence: 99%

Beneficial Effect of a Novel Diuretic, Ml7055, on Blood Pressure and Cardiovascular Hypertrophy in Spontaneously Hypertensive Rats

Shinkawa

Kato

Tsuchiya

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-We investigated the effects of a novel diuretic, M17055, on blood pressure and cardiovascular hypertrophy in spontaneously hypertensive rats (SHR). M17055 was orally administered once a day for 24 consecutive days to 14-week-old male SHR. M17055 at doses of 1.25, 2.5 and 5 mg/kg/day exerted a dose related diuretic and antihypertensive effect during the treatment. The weight of the left ventricle normalized by body weight on the following day of the last dosage was significantly (P<0.01) reduced by M17055 at doses of 2.5 and 5 mg/kg/day in a dose-dependent manner. The effect of M17055 on cardiac hypertrophy was more potent (P<0.01) than that of captopril, when the comparison was performed at the doses of M17055 and captopril inducing the same extent of blood-pressure decrement. Vascular hypertrophy was evaluated by the media/lumen ratio (M/L) in the thoracic aorta and the first branch of the superior mesenteric artery. In the aorta, M/L was slightly, but not significantly, decreased by M17055 at doses of 2.5 and 5 mg/kg/day, whereas it was decreased significantly (P <0.01) by captopril. In the mesenteric artery, the ratio was significantly (P<0.05) reduced by M17055 at a dose of 5 mg/kg/day. These results suggest that M17055 possesses beneficial properties for the clinical treatment of hypertension.

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Na+-K+ pump and Na+-K+ co-transport in cultured vascular smooth muscle cells from spontaneously hypertensive and normotensive rats

Cited by 29 publications

References 0 publications

Cell-volume-dependent vascular smooth muscle contraction: role of Na+, K+, 2Cl? cotransport, intracellular Cl? and L-type Ca2+ channels

Cell-volume-dependent vascular smooth muscle contraction: role of Na+, K+, 2Cl? cotransport, intracellular Cl? and L-type Ca2+ channels

Cellular Signalling by Lipoproteins in Cultured Smooth Muscle Cells from Spontaneously Hypertensive Rats

Beneficial Effect of a Novel Diuretic, Ml7055, on Blood Pressure and Cardiovascular Hypertrophy in Spontaneously Hypertensive Rats

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