Abstract. Aldosterone (Aldo) accelerates hypertension, proteinuria, and glomerulosclerosis in animal models of malignant hypertension or chronic renal failure. Aldo may exert these deleterious renal effects by elevating renal vascular resistance and glomerular capillary pressure. To test this possibility, directly examined were the action of Aldo on the afferent (Af) and efferent (Ef) arterioles (Arts). Examined were the effect of Aldo added to both the bath and lumen on the intraluminal diameter (measured at the most responsive point) of rabbits. Aldo caused dose-dependent constriction in both arterioles with a higher sensitivity in Ef-Arts. Vasoconstrictor action of Aldo was not affected by a mineralocorticoid receptor antagonist spironolactone and was reproduced by membrane-impermeable albumin-conjugated Aldo, suggesting that the vasoconstrictor actions are nongenomic. Pretreatment with neomycin (a specific inhibitor of phospholipase C) abolished the vasoconstrictor action of Aldo in both arterioles. In addition, the vasoconstrictor action of Aldo on Af-Arts was inhibited by both nifedipine and efonidipine, whereas that on Ef-Arts was inhibited by efonidipine but not nifedipine. The results demonstrate that Aldo causes nongenomic vasoconstriction by activating phospholipase C with a subsequent calcium mobilization thorough L-or T-type voltage-dependent calcium channels in Af-or Ef-Arts, respectively. These vasoconstrictor actions on the glomerular microcirculation may play an important role in the pathophysiology and progression of renal diseases by elevating renal vascular resistance and glomerular capillary pressure.There is increasing evidence that renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis and progression of renal diseases (1-5). Although angiotensin II (AngII) has been identified as the primary mediator of the system, recent studies have raised the possibility that aldosterone (Aldo), independent of renin-angiotensin, also participates in mediating renal injury (5-10). Greene et al. (7) have evaluated the ability of Aldo to reverse the renal protective effects of RAAS blockade in the 5/6 nephrectomy model of hypertension and glomerulosclerosis. They found that pharmacologic blockade of RAAS with angiotensin-converting enzyme inhibitor and AngII receptor blocker reduces plasma Aldo levels, systolic BP, proteinuria and renal lesions, all of which were reversed when Aldo was infused concurrently. Rocha et al. (8) also demonstrated that renal-protective effects of captopril, an angiotensin-converting enzyme inhibitor, were reversed by an Aldo infusion in stroke-prone spontaneously hypertensive rat (SHRSP), an animal model of malignant hypertension. They found that captopril treatment prevented the development of proteinuria and glomerular-renal vascular lesions with reducing endogenous Aldo levels, whereas subsequent Aldo infusion reversed these protective effects of captopril. Although the underlying mechanisms for these actions are not well defined, Aldo may e...

Abstract-We have recently demonstrated that aldosterone causes nongenomic vasoconstriction by activating phospholipase C (PLC) in the preglomerular afferent arteriole (Af-Art). In the present study, we tested the hypothesis that endothelium modulates this vasoconstrictor action by releasing nitric oxide (NO). In addition, to study the post-PLC mechanism, we examined possible contributions of phosphoinositol hydrolysis products. Rabbit Af-Arts were microperfused at 60 mm Hg in vitro, and increasing doses of aldosterone (10 Ϫ10 to 10 Ϫ8 mol/L) were added to the bath and lumen. Aldosterone caused dose-dependent vasoconstriction (within 10 minutes); significant (PϽ0.01) constriction was observed from 5ϫ10 Ϫ9 mol/L, and at 10 Ϫ8 mol/L, intraluminal diameter decreased by 29%Ϯ3% (nϭ9). Disrupting the endothelium augmented vasoconstriction; significant constriction was observed from 10 Ϫ10 mol/L, and at 10 Ϫ8 mol/L, the diameter decreased by 38%Ϯ2% (nϭ6). NO synthesis inhibition reproduced this augmentation (nϭ7). Pretreatment with chelerythrine (10 Ϫ6 mol/L), a protein kinase C (PKC) inhibitor, slightly attenuated the constriction; aldosterone at 10 Ϫ8 mol/L now decreased the diameter by 18%Ϯ3% (nϭ7). However, in Af-Arts treated with thapsigargin (10 Ϫ6 mol/L) or dantrolene (3ϫ10 Ϫ5 mol/L), which blocks inositol 1,4,5-triphosphate (IP 3 )-induced intracellular calcium release, aldosterone at 10 Ϫ8 mol/L decreased the diameter by only 9%Ϯ1% (nϭ6) or 9%Ϯ2% (nϭ5), respectively. These results demonstrate that in the Af-Art endothelium-derived NO modulates vasoconstrictor actions of aldosterone that are mediated by the activation of both IP 3 and PKC pathways. Such vasoconstrictor actions of aldosterone may contribute to the development or aggravation of hypertension by elevating renal vascular resistance in cardiovascular diseases associated with endothelium dysfunction.

These results suggest that exercise does not worsen renal function and has renal-protective effects in this model of rats. Moreover, the antihypertensive therapy has additional renal-protective effects in this model of rats.

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The results suggest that troglitazone has renoprotective effects in this rat model. These effects might be due to the inhibition of growth factors rather than to the minute hypotensive effect, although the mechanism remains to be elucidated.

With the development of nanotechnology, nanomaterials have been used in dental fields over the past years. Among them, graphene and its derivatives have attracted great attentions, owing to their excellent physicochemical property, morphology, biocompatibility, multi-differentiation activity, and antimicrobial activity. In our review, we summarized the recent progress about their applications on the dentistry. The synthesis methods, structures, and properties of graphene-based materials are discussed. Then, the dental applications of graphene-based materials are emphatically collected and described. Finally, the challenges and outlooks of graphene-based nanomaterials on the dental applications are discussed in this paper, aiming at inspiring more excellent studies.

A high-fructose diet (HFD) has been shown to elevate blood pressure (BP) and to decrease insulin sensitivity in rats. Although running exercise can attenuate these phenomena, its effect on target organ protection is not clear. We investigated whether exercise training has renal protective effects in this model. Nine-week-old spontaneously hypertensive rats were allocated to groups that received HFD or a control diet (control group) for 15 weeks. At the age of 10 weeks, fructose-fed rats were allocated to groups that were given vehicle (FRU group), temocapril, an angiotensin converting enzyme inhibitor (TEM group), exercise training (EX group; treadmill running), or temocapril plus exercise training (TEM+EX group). BP was higher in the FRU group than in the control group. Exercise training tended to decrease BP and temocapril treatment decreased BP significantly. Proteinuria was similar in the five groups. Plasma leptin concentration and epididymal fat weight were lower in the EX and TEM+EX groups than in the FRU group. In the soleus muscle of the FRU group, the composite ratio of type I fiber was decreased and that of type IIa fiber was increased compared with those in the control group. Both temocapril and exercise training restored these ratios. The glomerular sclerosis index (GSI) was higher in the FRU group than in the control group. GSI was decreased equally in the TEM, EX, and TEM+EX groups and was positively correlated with plasma leptin concentration. The results suggest that exercise training ameliorates glomerular sclerosis through mechanisms other than a reduction in BP.

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