The Relationship of Prorenin Values to Microvascular Complications in Patients with Insulin-Dependent Diabetes Mellitus

Davies, Linda; Fulcher, Greg; Atkins, Andrew; Frumar, Kim; Monaghan, J. C.; Stokes, Gordon S.; Clifton-Bligh, P; McElduff, Aidan; Robinson, Bruce G.; Stiel, J. N.; Twigg, Stephen M.; Wilmshurst, E. G.

doi:10.1016/s1056-8727(98)00020-8

Cited by 12 publications

(10 citation statements)

References 21 publications

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“…Progression of diabetes mellitus causes further accumulation of intracellular prorenin through inhibition of prorenin processing by transmural pressure, and the elevated intrarenal prorenin levels may lead to the increased plasma prorenin levels. These results could explain previous clinical reports demonstrating low renin and high prorenin levels in the blood of diabetics (1,(3)(4)(5)(6)(7).…”

Section: Discussionsupporting

confidence: 86%

Transmural Pressure Control of Prorenin Processing and Secretion in Diabetic Rat Juxtaglomerular Cells.

et al. 2003

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In diabetic patients, the elevation of plasma prorenin levels or arterial pressure is correlated with the severity of diabetic nephropathy. This study was designed to assess the effects of transmural pressure on prorenin regulation in juxtaglomerular (JG) cells from diabetes rats. The JG cells, harvested from rats intraperitoneally injected with streptozotocin 7 (early-diabetic) or 28 (late-diabetic) days previously, were exposed to atmospheric pressure (AP) and AP+40 mmHg for 12 h, and the renin secretion rate (RSR), prorenin secretion rate (PRSR), active renin content (ARC), prorenin content (PRC), and total renin content (TRC) were determined. Exposure of control JG cells to AP+40-mmHg significantly decreased RSR, PRSR, and ARC and significantly increased PRC without affecting TRC, suggesting the occurrence of pressure-mediated inhibition of prorenin processing and secretion. Exposure of early-diabetic and late-diabetic cells to AP+40-mmHg significantly decreased ARC and significantly increased PRC without affecting RSR, PRSR, or TRC. The changes in ARC and PRC were similar in the control and early-diabetic cells, but greater changes were observed in late-diabetic cells. However, when streptozotocin-treated rats were continuously treated with insulin (9 U/kg/day), the transmural pressure control of prorenin in JG cells was similar to that observed in the JG cells from control rats. In late-diabetic cells, treatment with a phospholipase C inhibitor did not alter the pressure control of ARC or PRC; however, treatment with a phospholipase D inhibitor did inhibit the changes in ARC and PRC with transmural pressure. Thus, pressure-mediated inhibition of prorenin secretion from JG cells has already been impaired in early diabetes. Pressure-induced inhibition of prorenin processing in JG cells via phospholipase D-dependent pathways is enhanced in late diabetes.

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Section: Discussionsupporting

confidence: 86%

Transmural Pressure Control of Prorenin Processing and Secretion in Diabetic Rat Juxtaglomerular Cells.

et al. 2003

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“…28 -30 This scenario would also account for the fact that prorenin predicts microvascular complications in patients with diabetes mellitus. [31][32][33] The recent identification of a binding site for renin and prorenin in human kidney mesangium and arteries has created a new interest in a role for prorenin in health and disease. 26 Until recently, prorenin, despite circulating at plasma concentrations 10-fold higher than those of renin, was thought to play a role in physiology only as a precursor to renin.…”

Section: ϫ2mentioning

confidence: 99%

Renal and Hormonal Responses to Direct Renin Inhibition With Aliskiren in Healthy Humans

et al. 2008

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Background-Pharmacological interruption of the renin-angiotensin system focuses on optimization of blockade. As a measure of intrarenal renin activity, we have examined renal plasma flow (RPF) responses in a standardized protocol. Compared with responses with angiotensin-converting enzyme inhibition (rise in RPF Ϸ95 mL · min Ϫ1 · 1.73 m Ϫ2 ), greater renal vasodilation with angiotensin receptor blockers (Ϸ145 mL · min Ϫ1 · 1.73 m Ϫ2 ) suggested more effective blockade. We predicted that blockade with the direct oral renin inhibitor aliskiren would produce renal vascular responses exceeding those induced by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Methods and Results-Twenty healthy normotensive subjects were studied on a low-sodium (10 mmol/d) diet, receiving separate escalating doses of aliskiren. Six additional subjects received captopril 25 mg as a low-sodium comparison and also received aliskiren on a high-sodium (200 mmol/d) diet. RPF was measured by clearance of para-aminohippurate. Aliskiren induced a remarkable dose-related renal vasodilation in low-sodium balance. The RPF response was maximal at the 600-mg dose (197Ϯ27 mL · min Ϫ1 · 1.73 m Ϫ2 ) and exceeded responses to captopril (92Ϯ20 mL · min Ϫ1 · 1.73 m

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“…in den Nieren, dem Herzen, den Augen, dem Gehirn und dem Fettgewebe vermittelt [6,9,15]. Man geht heute davon aus, dass die Aktivierung lokaler RAAS-Syste me in die Pathogenese von Erkrankungen wie Herzinsuffizienz, Diabetes mellitus, Retinopathie und Nephropathie involviert ist [7,10,11]. Die Effektivität einer therapeutischen RAAS-Blockade und die in der vorlie- [2].…”

Section: Diskussionunclassified

Status der Behandlung der arteriellen Hypertonie unter Praxisbedingungen in deutschen Arztpraxen zum Zeitpunkt der Einführung des Renininhibitors Aliskiren

et al. 2010

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According to the evaluation of primary care physicians participating in this study, aliskiren might be useful for antihypertensive treatment in patients with severe arterial hypertension, in patients with an already long-lasting course of disease, and in the presence of comorbidities such as diabetes mellitus. The high percentage of patients in this study cohort already treated with an ACE inhibitor or an AT(1) receptor blocker represents good adherence of primary care physicians to current treatment guidelines. The evaluation of loop diuretics as important antihypertensive drugs by 32.3% of attending physicians in this study requires critical discussion.

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The Relationship of Prorenin Values to Microvascular Complications in Patients with Insulin-Dependent Diabetes Mellitus

Cited by 12 publications

References 21 publications

Transmural Pressure Control of Prorenin Processing and Secretion in Diabetic Rat Juxtaglomerular Cells.

Transmural Pressure Control of Prorenin Processing and Secretion in Diabetic Rat Juxtaglomerular Cells.

Renal and Hormonal Responses to Direct Renin Inhibition With Aliskiren in Healthy Humans

Status der Behandlung der arteriellen Hypertonie unter Praxisbedingungen in deutschen Arztpraxen zum Zeitpunkt der Einführung des Renininhibitors Aliskiren

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