Relation of glomerular injury to preglomerular resistance in experimental hypertension

Olson, Jean L.; Wilson, Stephen K.; Heptinstall, R. H.

doi:10.1038/ki.1986.76

Cited by 70 publications

(37 citation statements)

References 33 publications

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“…Under normal circumstances, the moment-to-moment variations in mean systemic arterial pressure of up to 32 mmHg in the rat (52), are unlikely to induce significant changes in glomerular volume due to the precise autoregulation of intraglomerular pressure (53). However, in circumstances in which decreased preglomerular resistance and impaired or absent autoregulation of intraglomerular pressure exist, e.g., in residual glomeruli of the remnant kidney (53)(54)(55), in chronic passive Heymann glomerulonephritis (56) and in poorly controlled experimental diabetes (57), a more complete intraglomerular transmission of systemic arterial pressure and its oscillations is permitted. In these conditions, mean intraglomerular pressure variation caused by changes in systemic pressure may approach 10 mmHg (52,53).…”

Section: Discussionmentioning

confidence: 99%

Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.

Riser¹,

Cortés²,

Zhao³

et al. 1992

J. Clin. Invest.

244

139

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To define the interplay of glomerular hypertension and hypertrophy with mesangial extracellular matrix (ECM) deposition, we examined the effects of glomerular capillary distention and mesangial cell stretching on ECM synthesis. The volume of microdissected rat glomeruli (V ,), perfused ex vivo at increasing flows, was quantified and related to the proximal intraglomerular pressure (PIP). Glomerular compliance, expressed as the slope of the positive linear relationship between PIP and V was 7.68 x 103 gm3/mmHg. Total V, increment (PIP 0-150 mmHg) was 1.162 X 106 pm3 or 61% (n = 13). A 16% increase in V, was obtained over the PIP range equivalent to the pathophysiologial limits of mean transcapillary pressure difference. A similar effect of renal perfusion on V3 was also noted histologically in tissue from kidneys perfused/fixed in vivo. Cultured mesangial cells undergoing cyclic stretching increased their synthesis of protein, total collagen, and key components of ECM (collagen IV, collagen I, laminin, fibronectin). Synthetic rates were stimulated by cell growth and the degree of stretching. These results suggest that capillary expansion and stretching of mesangial cells by glomerular hypertension provokes increased ECM production which is accentuated by cell growth and glomerular hypertrophy. Mesangial expansion and glomerulosclerosis might result from this interplay of mechanical and metabolic forces. (J. Clin. Invest. 1992. 90:1932-1943

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Section: Discussionmentioning

confidence: 99%

Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.

Riser¹,

Cortés²,

Zhao³

et al. 1992

J. Clin. Invest.

244

139

View full text Add to dashboard Cite

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“…A great deal of experimental and clinical evidence has since been obtained in support of the concept (86,93). Moreover, although the concept was initially proposed in the context of target organ damage observed with severe or malignant hypertension, an association between preglomerular vasodilatation, increased P GC and progressive glomerulosclerosis even with moderate hypertension, was subsequently recognized in chronic kidney disease (CKD) models (9,10,77,118). The direct demonstration that, in addition to being vasodilated, the preglomerular vasculature of the 5/6 renal ablation model of CKD also exhibits impaired renal autoregulation provided a potential explanation for the greatly enhanced glomerular susceptibility to hypertensive injury seen in this model (21).…”

Section: Historical Perspectivesmentioning

confidence: 99%

Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms

Loutzenhiser

Griffin²,

Bidani³

2006

American Journal of Physiology-Regulatory, Integrative and Comp

233

244

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dani. Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms. Am J Physiol Regul Integr Comp Physiol 290: R1153-R1167, 2006. doi:10.1152/ajpregu.00402.2005.-When the kidney is subjected to acute increases in blood pressure (BP), renal blood flow (RBF) and glomerular filtration rate (GFR) are observed to remain relatively constant. Two mechanisms, tubuloglomerular feedback (TGF) and the myogenic response, are thought to act in concert to achieve a precise moment-by-moment regulation of GFR and distal salt delivery. The current view is that this mechanism insulates renal excretory function from fluctuations in BP. Indeed, the concept that renal autoregulation is necessary for normal renal function and volume homeostasis has long been a cornerstone of renal physiology. This article presents a very different view, at least regarding the myogenic component of this response. We suggest that its primary purpose is to protect the kidney against the damaging effects of hypertension. The arguments advanced take into consideration the unique properties of the afferent arteriolar myogenic response that allow it to protect against the oscillating systolic pressure and the accruing evidence that when this response is impaired, the primary consequence is not a disturbed volume homeostasis but rather an increased susceptibility to hypertensive injury. It is suggested that redundant and compensatory mechanisms achieve volume regulation, despite considerable fluctuations in distal delivery, and the assumed moment-by-moment regulation of renal hemodynamics is questioned. Evidence is presented suggesting that additional mechanisms exist to maintain ambient levels of RBF and GFR within normal range, despite chronic alterations in BP and severely impaired acute responses to pressure. Finally, the implications of this new perspective on the divergent roles of the myogenic response to pressure vs. the TGF response to changes in distal delivery are considered, and it is proposed that in addition to TGF-induced vasoconstriction, vasodepressor responses to reduced distal delivery may play a critical role in modulating afferent arteriolar reactivity to integrate the regulatory and protective functions of the renal microvasculature. renal microcirculation; afferent arteriole; myogenic; tubuloglomerular feedback ONE OF THE MOST STRIKING CHARACTERISTICS of the renal circulation is the ability of the kidney to maintain a constant renal blood flow (RBF) and glomerular filtration rate (GFR) as renal perfusion pressure is altered. The dual regulation of both RBF and GFR is achieved by proportionate changes in the preglomerular resistance and is believed to be mediated by two mechanisms, tubuloglomerular feedback (TGF) and the renal myogenic response. TGF involves a flow-dependent signal that is sensed at the macula densa and alters tone in the adjacent segment of the afferent arteriole via a mechanism that remains controversial but likely involves adenosine and/or ATP (30,80,144). The myo...

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“…In SHR kidneys, glomerular injury is most prevalent in juxtamedullary nephrons, whereas pathological changes are much less apparent in superficial glomeruli. 26 - 27 In addition, Feld et al 26 demonstrated that urinary protein excretion is elevated in SHR, whereas albumin clearance in superficial nephrons appears normal, suggesting that proteinuria derives mainly from juxtamedullary nephrons. Furthermore, the distribution of the glomerular injury in SHR also corresponds to differences in intrarenal hemodynamics.…”

Section: Altered Pressure Response Of the Interiobular Artery In Sponmentioning

confidence: 99%

Enhanced myogenic responsiveness of renal interlobular arteries in spontaneously hypertensive rats.

1992

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We recently demonstrated that the interlobular artery (ILA) constricts in response to elevating renal arterial pressure (RAP), suggesting that the ILA contributes to renal autoregulation. In the present study, we examined the segmental myogenic responsiveness of the ILA in kidneys from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The tapered nature of the ILA allowed us to characterize the regional responsiveness, using the basal diameter to define segments as either proximal (greater than 60 fim), intermediate ( 2 We have previously demonstrated that myogenic afferent arteriolar vasoconstriction is reset to higher renal arterial pressure (RAP) levels in spontaneously hypertensive rats (SHR).3 Although the afferent arteriole is primarily responsible for both acute 4 -5 and chronic 6 ' 7 adaptations to elevated RAP, the interlobular artery (ILA) may also contribute to renal autoregulation. 8 ' 9 The involvement of the ILA in chronic adaptations of the renal vasculature to hypertension has not been previously examined.

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Relation of glomerular injury to preglomerular resistance in experimental hypertension

Cited by 70 publications

References 33 publications

Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.

Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.

Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms

Enhanced myogenic responsiveness of renal interlobular arteries in spontaneously hypertensive rats.

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