Abnormal Biochemistry of Vascular Smooth Muscle Plasma Membrane as an Important Factor in the Initiation and Maintenance of Hypertension in Rats

Kwan, Chiu‐Yin; Belbeck, L.; Daniel, E. E.

doi:10.1159/000158214

Cited by 40 publications

(46 citation statements)

References 21 publications

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“…Moreover, decreased calcium binding to vascular smooth muscle membranes has been associated with reduced membrane stabilization capacity, thus leading to an increase in membrane permeability to calcium and other ions. 15 " 17 Another abnormality described both in spontaneously hypertensive rats 18 and in the erythrocytes of patients with essential hypertension 19 consists in a reduced adenosine 5'-triphosphate (ATP)-dependent accumulation of calcium in cell membrane vesicles, indicating the existence of a reduced calmodulin-Ca 2+ -ATPase interaction. This abnormality leads to a reduction in calcium extrusion across the cell membranes.…”

Section: Plateletmentioning

confidence: 99%

Increased basal and thrombin-induced free calcium in platelets of essential hypertensive patients.

Lechi¹,

Lechi²,

Bonadonna³

et al. 1987

Hypertension

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SUMMARY Intracellular free calcium, [Ca 2 + ],, was studied in platelets of essential hypertensive subjects and normotensive controls under basal conditions and after stimulation with epinephrine, norepinephrine, angiotensin II, ouabain, and thrombin, using the fluorescent calcium indicator quin 2. Basal [Ca 2+ ], was significantly higher in hypertensive subjects (n = 32) than in normotensive controls (n = 30; 167.4 ± 5.0 vs 143.2 ± 3.1 nmol/L; p<0.001). Epinephrine, norepinephrine, angiotensin II, and ouabain had no effect on platelet calcium, whereas thrombin induced a dose-dependent increase in [Ca 2+ ]| in both the presence and absence of extracellular calcium. This [Ca 2+ ]| increase in the presence of extracellular calcium, which depends mainly on calcium influx, was significantly higher (p<0.05) in platelets of hypertensive subjects at all thrombin concentrations (ranging from 0.025-0.1 U/ml), while the [Ca 2+ ]| increase in the absence of extracellular calcium, which depends only on release from intracellular stores, was similar in hypertensive subjects and controls. These results suggest that, in essential hypertension, there is not only increased platelet resting [Ca 2+ ]| but also an increase in agonist-mediated calcium influx, which appears to indicate a cell membrane abnormality in the platelets of subjects with essential hypertension.

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Section: Plateletmentioning

confidence: 99%

Increased basal and thrombin-induced free calcium in platelets of essential hypertensive patients.

Lechi¹,

Lechi²,

Bonadonna³

et al. 1987

Hypertension

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“…48 A decreased ATP-dependent calcium accumulation by plasma membrane-enriched fractions isolated from arteries of SHRs has also been reported. 49 It is not yet known whether the calmodulindependent activity of this smooth muscle plasma membrane Ca 2+ ATPase is altered in hypertension. However, in erythrocytes and platelets from SHRs and patients with essential hypertension, a depressed calmodulin-dependent Ca 2+ ATPase activity has been found.…”

mentioning

confidence: 99%

Vascular smooth muscle cell calcium fluxes. Regulation by angiotensin II and lipoproteins.

et al. 1993

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This study examined 4SCa uptake, 45 Ca efflux, and the distribution of exchangeable 4SCa in confluent, quiescent cultures of aortic smooth muscle cells (VSMCs) from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). These parameters were investigated under basal conditions and after addition of angiotensin II (Ang II) and low (LDL) (Ang II) 1 is an important regulator / \ not only of vascular smooth muscle contraction A. A . but also of vascular smooth muscle cell (VSMC) growth (see References 1 and 2 for reviews). In hypertension, both the functional and structural integrity of vascular smooth muscle are deranged, 12 thus invoking an essential involvement of Ang II in the pathophysiology of hypertension. This is supported by observations that angiotensin converting enzyme inhibitors effectively lower blood pressure 3 and also prevent myointimal proliferation after vascular injury. 4 Hypertension greatly increases the frequency of atherosclerotic cardiovascular sequelae, and lipoproteins greatly affect the impact of hypertension on the pace of atherogenesis (see References 5 and 6 for reviews). The two diseases are closely linked with respect to predisposing risk factors, clinical manifestations, and vascular/cellular pathobiology; thus, the fundamental role of lipoproteins in the atherosclerotic process suggests that they may also be involved in the pathophysiology of hyper- tension. 5-6 Evidence is accumulating to indicate that low density lipoprotein (LDL) and high density lipoprotein (HDL) can influence smooth muscle cell processes that are distinct from those related to cholesterol homeostasis per se, such as growth-related metabolic events, cell morphology, and proliferation and contractile processes (reviewed in Reference 7).Calcium is a pivotal signaling molecule in the regulation of smooth muscle structure and function, and the hypothesis on the involvement of abnormalities of intracellular calcium handling in the pathophysiology of hypertension is based on the following principal observations.

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“…1), which would independently predict such an increase in fluidity in the SHR (52). Parenthetically, studies in blood vessels (14,15), myocytes (16,17), and erythrocytes (18) recently demonstrated that such activities are indeed present in the rat intestine (66), alterations of which could conceivably be responsible for the fatty acid compositional differences.…”

Section: Discussionmentioning

confidence: 96%

“…In view of the recently reported differences in membrane fluidity, structure, phospholipid metabolism (10-13), and membrane Ca handling (14)(15)(16)(17)(18) between the SHR and WKy control, and in view of the postulated role of altered membrane lipid composition in Ca transport (19-28), we evaluated whether small intestinal brush border membrane in the SHR is characterized by changes in fluidity and lipid content. Our data revealed an increase in lipid fluidity of the SHR membrane as measured by several different probes (Table II) and at a time before hypertension was detectable.…”

Section: Discussionmentioning

confidence: 99%

“…Three lines of evidence suggest this may be the case. First, changes in membrane fluidity (10), membrane structure (11), membrane inositol phospholipid metabolism (12,13), and alterations in "5Ca uptake, binding, and/or permeability (14)(15)(16)(17)(18) have been described in SHR as compared to normotensive Wistar-Kyoto (WKy) controls. Second, in models of phospholipid bilayers, permeability to Ca has been correlated with changes in lipid composition and fluidity (19,20).…”

Section: Introductionmentioning

confidence: 99%

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Increased calcium absorption in prehypertensive spontaneously hypertensive rat. Role of serum 1,25-dihydroxyvitamin D3 levels and intestinal brush border membrane fluidity.

Lau¹,

Langman²,

Gafter³

et al. 1986

J. Clin. Invest.

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Changes in Ca absorption have been described in the spontaneously hypertensive rat (SHR) compared with Wistar-Kyoto (WKy) rats. In 3.5-wk-old SHR and age-matched WKy controls, we measured direct arterial blood pressure, Ca absorption, and serum 1,25-dihydroxyvitamin D3 11,25(OH)2D31 levels and small intestine brush border membrane (BBM) fluidity and lipid composition. The two objectives were (a) to define the nature of the absorptive changes before detectable hypertension and (b) to evaluate the potential mechanism(s). We found that even at this normotensive stage (106±4 vs. 107±2 torr for the female and 109±3 vs. 104±3 torr for the male), the SHR (a) absorbed more Ca (1.46±0.06 vs. 1.14±0.08 mmol/d and 1.53±0.06 vs. 1.28±0.06 mmol/d, respectively) and retained more Ca, (b) had higher serum 1,25(OH)D3 levels (340±36 vs. 160±18 pg/ml and 230±25 vs. 150±16 pg/ml, respectively), and (c) possessed BBM with increased fluidity and with reduced fatty acyl saturation index owing to decreased stearic (32.2±2.6% vs. 38.2±0.9%) but increased linoleic acids (12.2±2.0% vs. 7.6±1.6%). These results demonstrate increased Ca absorption in prehypertensive SHR associated with increased serum 1,25(OH)2D3 levels, increased intestinal BBM fluidity, and reduced saturation index, which singly or in combination could produce the changes in intestinal Ca transport.

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Abnormal Biochemistry of Vascular Smooth Muscle Plasma Membrane as an Important Factor in the Initiation and Maintenance of Hypertension in Rats

Cited by 40 publications

References 21 publications

Increased basal and thrombin-induced free calcium in platelets of essential hypertensive patients.

Increased basal and thrombin-induced free calcium in platelets of essential hypertensive patients.

Vascular smooth muscle cell calcium fluxes. Regulation by angiotensin II and lipoproteins.

Increased calcium absorption in prehypertensive spontaneously hypertensive rat. Role of serum 1,25-dihydroxyvitamin D3 levels and intestinal brush border membrane fluidity.

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