J Am Soc Nephrol. Aliskiren Clinical Trials. Clin Pharmacokinet.
In PD group, IR was increased since it was negative in the epithelium, weak in the basal cell layer, and moderate in the lamina propria of the gingival epithelium Figure 4e. Both types of drugs inhibit the formation of aldosterone, a hormone, which has been shown to have harmful effects on patients with chronic heart and kidney disorders. It is characterized by a chronic infection leading to destruction of periodontal tissues, resulting in loss of connective soft tissue and bone and formation of periodontal pockets that eventually cause teeth loss Okada and Murakami, ; Bascones-Martinez et al. Aliskiren reduces blood pressure and suppresses plasma renin activity in combination with a thiazide diuretic, an angiotensin-converting enzyme inhibitor, or an angiotensin receptor blocker.
This might be promoting a down regulation of ACE due to feedback mechanism, as shown by previous other studies Schunkert et al. Concomitant use of aliskiren with cyclosporine is not recommended. Although it is speculative, the higher AT1R and AT2R expression and protein production seen in the gingival tissue of normal and diabetic mice after PD can be happening because of increased cytokine and chemokine release by gingival fibroblast, thereby increasing AngII production by acting on their specific receptors Forrester et al. Optimization of this compound by Novartis led to the development of aliskiren — the only direct renin inhibitor which is clinically used as an antihypertensive drug.
Thus, our results highlight, for the first time, the hypothesis that RAS might be contributing to the periodontal bone loss of diabetic mice after PD. However, they were anesthetized and manipulated similarly to undergo the same stress as the others. This is possible as Alisk might be blocking the generation of AngI from AGT by causing renin inhibition, thereby reducing all angiotensin peptides.
Structure-based design of aliskiren: A novel orally effective renin inhibitor. Both types of drugs inhibit the formation of aldosterone, a hormone, which has been shown to have harmful effects on patients with chronic heart and kidney disorders.
Aliskiren has good water solubility and low lipophilicity, and is resistant to biodegradation by peptidases in the intestine, blood circulation, and the liver. Pre-treatment of the Alisk did not modify IR in the whole gingival tissue Figure 4f. As expected diabetic mice presented more severe periodontal destruction compared to normal mice with PD Figure 1C, D, and G. IR for renin was found in gingival tissue of control normal mice but not in diabetic mice, but mRNA expression was undetectable. Drugs with no clinically significant effects: Coadministration of lovastatin, atenolol, warfarin, furosemide, digoxin, celecoxib, hydrochlorothiazide, ramipril, valsartan, metformin, and amlodipine did not result in clinically significant increases in aliskiren exposure.
However, this needs further investigation. Greater reductions in blood pressure have been achieved when aliskiren was used in combination with hydrochlorothiazide or an angiotensin-receptor blocker. Dzau VJ.
Prognostic value of hour blood pressure variability. Kostis JB. Angiotensin II also has a direct vasoconstrictive effect, which increases BP, and promotes inflammation and remodeling of the cardiovascular system, which leads to thrombosis or left ventricular hypertrophy. Addition of Alisk inhibited the IR in the epithelium but did not change it in the basal cell layer and lamina propria of the gingival tissue of normal mice Figure 4g. PD increased the IR in the epithelium but maintained in the basal cell layer and lamina propria Figure 4g. However, they were anesthetized and manipulated similarly to undergo the same stress as the others.
Functional importance of angiotensin-converting enzyme-dependent in situ angiotensin II generation in the human forearm.