Lower Na+- H+ antiport activity in vascular smooth muscle cells of Wistar???Kyoto rats than spontaneously hypertensive and Wistar rats

1990 ◽  
Vol 8 (9) ◽  
pp. 867-871 ◽  
Author(s):  
Daniel Alexander ◽  
Jeffrey P. Gardner ◽  
Haruo Tomonari ◽  
Burton P. Fine ◽  
Abraham Aviv
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Wistar Rats ◽  
Muscle Cells ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Wistar Kyoto

scholarly journals RACK1 regulates angiotensin II-induced contractions of SHR preglomerular vascular smooth muscle cells

2017 ◽  
Vol 312 (4) ◽  
pp. F565-F576 ◽  
Author(s):  
Xiao Zhu ◽  
Edwin K. Jackson
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Scaffolding Protein ◽  
Cell Fractionation ◽  
Ang Ii ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

The preglomerular microcirculation of spontaneously hypertensive rats (SHR) is hypersensitive to angiotensin (ANG) II, and studies have shown that this is likely due to enhanced coincident signaling between G protein subunits αq (Gαq; released by ANG II) and βγ (Gβγ; released by Gi-coupled receptors) to active phospholipase C (PLC). Here we investigated the molecular basis for the enhanced coincident signaling between Gβγ and Gαq in SHR preglomerular vascular smooth muscle cells (PGVSMCs). Because receptor for activated C kinase 1 (RACK1; a scaffolding protein) organizes interactions between Gβγ, Gαq, and PLC, we included RACK1 in this investigation. Cell fractionation studies demonstrated increased levels of membrane (but not cytosolic) Gβ, Gαq, PLCβ3, and RACK1 in SHR PGVSMCs compared with Wistar-Kyoto rat PGVSMCs. In SHR PGVSMCs, coimmunoprecipitation demonstrated RACK1 binding to Gβ and PLCβ3, but only at cell membranes. Pertussis toxin (which blocks Gβγ) and U73122 (which blocks PLC) reduced membrane RACK1; however, RACK1 knockdown (shRNA) did not affect membrane levels of Gβ, Gαq, or PLCβ3. In a novel gel contraction assay, RACK1 knockdown in SHR PGVSMCs attenuated contractions to ANG II and abrogated the ability of neuropeptide Y (which signals via Gβγ) to enhance ANG II-induced contractions. We conclude that in SHR PGVSMCs the enlarged pool of Gβγ and PLCβ3 recruits RACK1 to membranes and RACK1 then organizes signaling. Consequently, knockdown of RACK1 prevents coincident signaling between ANG II and the Gi pathway. This is the first study to implicate RACK1 in vascular smooth muscle cell contraction and suggests that RACK1 inhibitors could be effective cardiovascular drugs.

Blunted cGMP response to ANF in vascular smooth muscle cells of SHR

1988 ◽  
Vol 255 (5) ◽  
pp. C573-C580 ◽  
Author(s):  
M. Nakamura ◽  
A. Nakamura ◽  
B. Fine ◽  
A. Aviv
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Spontaneously Hypertensive Rat ◽  
Specific Binding ◽  
Poor Response ◽  
Muscle Cells ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

Abnormalities in the coupling of atrial natriuretic factor (ANF) receptors with the guanosine 5'-cyclic monophosphate (cGMP) system in vascular smooth muscle cells (VSMCs) may play a role in the pathophysiology of hypertension in the spontaneously hypertensive rat (SHR). This concept was examined in cultured, aortic VSMCs (passages 6-10) from SHR, Wistar-Kyoto (WKY), and American Wistar (Wis) rats. Quiescent VSMCs of the SHR (serum deprived for 24 h) had higher ANF receptor density (Bmax) and lower affinity [i.e., increased equilibrium dissociation constant (Kd)] than cells from normotensive controls. Maximal binding (Bmax) (specific binding sites/cell) values for these cells were SHR 112,855 +/- 6,951, WKY 48,650 +/- 3,607, and Wis 36,122 +/- 2,607 (means +/- SE; P less than 0.001 for SHR vs. both WKY and Wis). The Kd values were (in nM) SHR 1.20 +/- 0.098, WKY 0.657 +/- 0.065, and Wis 0.37 +/- 0.037 (P less than 0.001 for SHR vs. both WKY and Wis). Despite their higher Bmax, VSMCs of the SHR showed a substantially lower maximal stimulation of cGMP accumulation in response to ANF: 987 +/- 29.3, 1,992 +/- 574.2, and 2,019 +/- 273.8 fmol.4 min-1.10(6) cells-1 for SHR, WKY, and Wis, respectively (P less than 0.01 for SHR vs. Wis and P less than 0.02 for SHR vs. WKY). Further experiments demonstrated that the poor response of SHR VSMCs to the ANF was not due to a population of receptors that did not couple to the particulate guanylate cyclase. Such findings demonstrate a dissociation of the cGMP response to ANF from the binding of the hormone to its receptors in VSMCs of the SHR compared with controls. This appears to represent a primary and innate defect in these cells that may contribute to the hypertensive process in the SHR.

Reduced Cytosolic Free Sodium Concentration in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats

1994 ◽  
Vol 86 (6) ◽  
pp. 741-747
Author(s):  
Martin Tepel ◽  
JAN Holthues ◽  
Marcus Neusser ◽  
Petra Golinski ◽  
Zhiming Zhu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Spontaneously Hypertensive Rats ◽  
Muscle Cells ◽  
Sodium Concentration ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

1. Cytosolic free sodium concentration and sodium transport systems were measured in intact cultured vascular smooth muscle cells from spontaneously hypertensive rats of the Münster strain and from normotensive Wistar—Kyoto rats using the sodium-sensitive fluorescent dye sodium-binding benzofuran isophthalate. 2. Resting cytosolic free sodium concentration was significantly lower in vascular smooth muscle cells from spontaneously hypertensive rats than from Wistar-Kyoto rats (10.2 ± 1.5 mmol/l, n = 26, versus 19.4 ± 2.5 mmol/l, n = 20, P < 0.01). 3. Inhibition of Na+, K+-ATPase by ouabain caused a dose-dependent increase in cytosolic free sodium concentration in spontaneously hypertensive rats and Wistar—Kyoto rats. 4. Activation of Na+-Ca2+ exchange by ionomycin increased cytosolic free sodium concentration in both strains. However, the ionomycin-induced increase in cytosolic free sodium concentrations was significantly higher in vascular smooth muscle cells from spontaneously hypertensive rats than from Wistar—Kyoto rats (220 ± 35% of the resting cytosolic free sodium concentration versus 148 ± 27%; P < 0.05). The ionomycin-induced increase in cytosolic free sodium concentration was prevented in the absence of external sodium or by inhibition of Na+-Ca2+ exchange by NiCl2. 5. Activation of Na+-H+ exchange by intracellular acidification of vascular smooth muscle cells with propionic acid increased cytosolic free sodium concentration in each strain (19.6 ± 5.7 versus 16.3 ± 3.2 mmol/l). 6. It is concluded that concepts concerning the role of cytosolic free sodium concentration in the pathogenesis of primary hypertension need to be reinvestigated. However, the conclusions from results obtained in cultured vascular smooth muscle cells are limited with respect to conditions in vivo.

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