Effect of Age on Noradrenaline Sensitivity of Mesenteric Resistance Vessels in Spontaneously Hypertensive and Wistar—Kyoto Rats

1979 ◽  
Vol 57 (s5) ◽  
pp. 43s-45s ◽  
Author(s):  
M. J. Mulvany ◽  
C. Aalkjær ◽  
J. Christensen
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Nerve Terminals ◽  
Spontaneously Hypertensive ◽  
Resistance Vessels ◽  
Uptake Of Noradrenaline ◽  
Wistar Kyoto ◽  
Effect Of Age

1. We have compared the noradrenaline sensitivity of 150 μm arterial resistance vessels taken from a specific place in the mesenteric bed of spontaneously hypertensive (SH) rats and of control Wistar—Kyoto (WK) rats at three ages: 6 weeks, 12 weeks and 24 weeks. 2. The noradrenaline sensitivity of the vessels under normal conditions was the same at all ages in both SH and WK rats (ED50 about 3 μmol/l). 3. After addition of cocaine (which inhibits the uptake of noradrenaline in the nerve terminals) all vessels became more sensitive to noradrenaline, but at all ages the increase in sensitivity was greater in the vessels of SH rats, suggesting that the smooth muscle cells in these vessels had a greater intrinsic noradrenaline sensitivity than the vessels of WK rats. 4. Since elevation of the blood pressure in the SH rats occurs mainly between the ages of 6 and 12 weeks, the results suggest that the greater intrinsic smooth muscle cell sensitivity of the SH rat vessels is a factor which is amongst the primary factors responsible for the development of hypertension in the SH rat.

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.

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