Renal phospholipase C and diglyceride lipase activity in spontaneously hypertensive rats.

Kawaguchi, Hideaki; Okamoto, Hiroshi; Saitô, Hiroshi; Yasuda, Hisakazu

doi:10.1161/01.hyp.10.1.100

Cited by 19 publications

(5 citation statements)

References 28 publications

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“…PLA, activity, by contrast, was not elevated in SHRs and was not correlated with BP. Similar increases in basal PLC have been reported in nonvascular tissues of SHRs including red blood cells (45), platelets (82), and kidney (46).…”

Section: Spontaneously Hypertensive Ratsupporting

confidence: 80%

Function of the PI Cycle in Arterial Smooth Muscle During Hypertension

Deth

1991

Cardiovascular Drug Reviews

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After the early work of Berridge ( 1 1) and Nishizuka (60) which focused attention on the involvement of inositol-1,4,5-trisphosphate ( 1 ,4,5-IP3) and diacylglycerol (DAG) in causing Ca'+ release and protein kinase C activation, respectively, there have been a number of studies demonstrating the presence of these mechanisms in vascular preparations. At the same time, studies of vascular function during hypertension have begun to identify alterations in phosphoinositol (PI) cycle activity that may indicate its involvement in the genesis or maintenance of the hypertensive state. This article is intended to review current evidence for the role of the PI cycle in regulating vascular contractility and the possible abnormalities in cycle activity that may accompany hypertension. FUNCTIONAL ROLE OF THE PI CYCLE IN ARTERIAL SMOOTH MUSCLEIn its basic form, the PI cycle consists of the phospholipase C (PLC)-catalyzed hydrolysis of inositol phospholipids (PI, PIP, and PIP,) and their resynthesis from DAG, ATP, and inositol. The basal level of phospholipase activity is augmented by one or several GTP-binding G proteins that are in turn activated by agonist-binding receptors such as a,-adrenergic or angiotensin 11. Figure 1 provides an outline of PI cycle events, including several of the regulatory mechanisms that are discussed below.While the basic agonist-stimulated PI cycle described above is well described and fairly straightforward, its dynamic function is now recognized to be more complex. We know that there is variety and control at the level of polyphosphoinositide synthesis such that different phospholipids must be considered substrates for phospholipase-dependent second messenger formation. A larger number of different inositol phosphates are produced either directly from phospholipid hydrolysis or indirectly through metabolic pathways. In most cases, their roles are not well understood. Both the receptor-induced stimulation of

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Section: Spontaneously Hypertensive Ratsupporting

confidence: 80%

Function of the PI Cycle in Arterial Smooth Muscle During Hypertension

Deth

1991

Cardiovascular Drug Reviews

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“…However, consistent with our findings, there is a report of increased phospholipase C activity in SHR compared with WKY rats. 23 The result of this study cannot identify the specific sites of renal DA-1 receptor phospholipase C signal transduction pathway that are affected in the adult SHR. However, it is possible that the sites involved are distal to the dopamine receptors, since there are reports that showed no differences in renal tubular DA-1 receptor number, distribution, or affinity between WKY rats and SHR of this age, 10 -17 although in 32-week-old SHR, the renal tubular DA-1 receptors were reported to be decreased.…”

Section: Discussionmentioning

confidence: 85%

Diminished phospholipase C activation by dopamine in spontaneously hypertensive rats.

et al. 1992

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It is reported that a defect in dopamine-1 (DA-1) receptor adenylate cyclase coupling in the proximal convoluted tubule in the spontaneously hypertensive rat may contribute to the diminished natriuretic response to DA-1 receptor agonists. Since the tubular DA-1 receptor is also coupled to phospholipase C, and both of these cellular signaling processes are involved in DA-1 receptor-mediated diuresis and natriuresis, it is important to know whether a similar defect is also present in DA-1 receptor-coupled phospholipase C pathway. The present study was therefore designed to determine the functional status of DA-1 receptor-phospholipase C coupling system of adult spontaneously hypertensive rats using a renal cortical slice preparation. In addition, the renal response to exogenously administered dopamine (1 /ig/kg/min i.v.) was also determined. We found that basal phospholipase C activity was significantly higher in hypertensive rats than in age-matched Wistar-Kyoto rats (7J6±0J2% versus 5.61±0.27%, p<0.05). However, compared with the normotensive controls, dopamine-induced increases in phospholipase C activity were significantly attenuated in the preparations of hypertensive rats in a concentration-dependent manner (13±6% versus 38±6% for 1 mM dopamine, p<0.05; 49±6% versus 71±9% for 3 mM dopamine, p<0.05; 50±16% versus 106±22%, p<0.05 for 10 mM dopamine). The diminished dopamine-induced phospholipase C activation was due to a deficiency in dopamine receptor-phospholipase coupling since the DA-1 receptor antagonist SCH 23390 (30 /iM), which blocked 50% of dopamine-induced inositol phosphate production in the Wistar-Kyoto rats, did not exert such an effect in the spontaneously hypertensive rats. The in vivo functional study showed that the diuretic and natriuretic responses to intravenous administration of dopamine were significantly diminished in spontaneously hypertensive rats compared with Wistar-Kyoto rats (urine output, 34± 1 versus 63±10 fil/30 min,p<0.05; urinary sodium excretion, 1.8±0.1 versus 3.2±0.2 ^teq/30 min,/x0.05). These results suggest that there is a defect in the tubular DA-1 receptor-phospholipase C coupling process in spontaneously hypertensive rats that may contribute to a diminished natiiuretic response to DA-1 receptor activation. (Hypertension 1992;19:102-108) I t is generally accepted that an abnormality in renal handling of sodium is one of the factors in the pathogenesis and/or maintenance of high blood pressure in genetic hypertension. Central to this assumption are the observations that spontaneously hypertensive rats (SHR), as opposed to their normotensive Wistar-Kyoto (WKY) counterparts, retain sodium avidly before the development of hypertension 1 and that urinary sodium excretion (U Na V) in SHR is normal or subnormal despite the presence of elevated blood pressure.2 Furthermore, dietary sodium restriction retards the development of hypertension in SHR.

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“…This could occur if the local production of these metabo lites were elevated in the renal vasculature of SHR or the degradation rate of cytochrome P-450 arachidonic acid metabolites in renal cortical tissue were reduced. In addi tion, Kawaguchi et al [24] have reported that phospholi pase A and C activity is enhanced in the kidney of adult SHR. Enhanced phospholipase activity could alter the production of cytochrome P-450 metabolites of arachi donic acid by elevating substrate availability independent of any differences in cytochrome P-450 activity.…”

Section: Discussionmentioning

confidence: 95%

Role of Cytochrome P-450 in Elevating Renal Vascular Tone in Spontaneously Hypertensive Rats

Gebremedhin

Imig

et al. 1993

J Vasc Res

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The contribution of cytochrome P-450 metabolites of arachidonic acid in elevating vascular tone in the kidneys of adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was examined using a juxtamedullary nephron microvascular preparation perfused in vitro with a physiological salt solution containing 5% albumin. At 80 mm Hg, the basal internal diameters of arcuate and interlobular arteries and proximal and distal afferent arterioles of the SHR averaged 341 ± 15.81 ± 5.24 ± 0.5 and 19 ± 0.3 µm, respectively. These diameters were 5-29% smaller (p < 0.05) than those measured in corresponding vessels in WKY rats. Addition of the P-450 inhibitors, ketoconazole (100 µM) or 17-octadecynoic acid (17-ODYA, 20 µM), to the perfusate and bath increased the diameters of the preglomerular vasculature of the SHR by 6-29%, but by only 3-13% in WKY rats and reduced significantly the differences in pressure-diameter relations between the two groups. The rate of formation of 20-hydroxyeicosatetraenoic acid (20-HETE) by renal cortical microsomes was similar in SHR and WKY rats. However, the production of epoxyeicosatrienoic acids (EETs) by cortical microsomes was 87% lower and dihydroxyeicosatrienoic acids (DHETs) 70% higher in the SHR than WKY rats. Ketoconazole (100 µM) reduced the formation of 20-HETE by 80%, and EETs and DHETs production by more than 98% in SHR and WKY rats. 17-ODYA (20 µM) reduced the formation of 20-HETE, EETs and DHETs by more than 98% in both groups. These results suggest that cytochrome P-450 metabolites of arachidonic acid contribute to the elevated renal vascular tone in adult SHR. This may be due to an enhanced vascular responsiveness to vasoconstrictor P-450 metabolites in SHR or an elevated local production of vasoconstrictor eicosanoids in the renal vasculature of SHR rather than in renal cortical tissue.

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Renal phospholipase C and diglyceride lipase activity in spontaneously hypertensive rats.

Cited by 19 publications

References 28 publications

Function of the PI Cycle in Arterial Smooth Muscle During Hypertension

Function of the PI Cycle in Arterial Smooth Muscle During Hypertension

Diminished phospholipase C activation by dopamine in spontaneously hypertensive rats.

Role of Cytochrome P-450 in Elevating Renal Vascular Tone in Spontaneously Hypertensive Rats

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