Protective Effects of Nanoparticle-Loaded Aliskiren on Cardiovascular System in Spontaneously Hypertensive Rats.
Amides
/ administration & dosage
Animals
Antihypertensive Agents
/ administration & dosage
Biomarkers
Blood Pressure
/ drug effects
Cardiovascular System
/ drug effects
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Carriers
/ chemistry
Fumarates
/ administration & dosage
Heart
/ drug effects
Hypertension
/ diagnosis
Nanoparticles
/ chemistry
Nitric Oxide
/ metabolism
Polyesters
/ chemistry
Rats
Rats, Inbred SHR
PLA nanoparticles
aliskiren
aorta
collagen
heart
hypertension
nitric oxide
renin
vasoactivity
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
25 Jul 2019
25 Jul 2019
Historique:
received:
29
05
2019
revised:
19
07
2019
accepted:
22
07
2019
entrez:
28
7
2019
pubmed:
28
7
2019
medline:
3
1
2020
Statut:
epublish
Résumé
Aliskiren, a renin inhibitor, has been shown to have cardioprotective and blood pressure (BP) lowering effects. We aimed to determine the effects of nanoparticle-loaded aliskiren on BP, nitric oxide synthase activity (NOS) and structural alterations of the heart and aorta developed due to spontaneous hypertension in rats. Twelve week-old male spontaneously hypertensive rats (SHR) were divided into the untreated group, group treated with powdered or nanoparticle-loaded aliskiren (25 mg/kg/day) and group treated with nanoparticles only for 3 weeks by gavage. BP was measured by tail-cuff plethysmography. NOS activity, eNOS and nNOS protein expressions, and collagen content were determined in both the heart and aorta. Vasoactivity of the mesenteric artery and wall thickness, inner diameter, and cross-sectional area (CSA) of the aorta were analyzed. After 3 weeks, BP was lower in both powdered and nanoparticle-loaded aliskiren groups with a more pronounced effect in the latter case. Only nanoparticle-loaded aliskiren increased the expression of nNOS along with increased NOS activity in the heart (by 30%). Moreover, nanoparticle-loaded aliskiren decreased vasoconstriction of the mesenteric artery and collagen content (by 11%), and CSA (by 25%) in the aorta compared to the powdered aliskiren group. In conclusion, nanoparticle-loaded aliskiren represents a promising drug with antihypertensive and cardioprotective effects.
Identifiants
pubmed: 31349653
pii: molecules24152710
doi: 10.3390/molecules24152710
pmc: PMC6695910
pii:
doi:
Substances chimiques
Amides
0
Antihypertensive Agents
0
Biomarkers
0
Drug Carriers
0
Fumarates
0
Polyesters
0
Nitric Oxide
31C4KY9ESH
poly(lactide)
459TN2L5F5
aliskiren
502FWN4Q32
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Références
Chem Biol. 2000 Jul;7(7):493-504
pubmed: 10903938
Int J Pharm. 2002 Jun 4;239(1-2):113-20
pubmed: 12052696
J Control Release. 2002 Oct 30;83(3):401-14
pubmed: 12387948
Crit Rev Ther Drug Carrier Syst. 2004;21(5):387-422
pubmed: 15719481
Clin Sci (Lond). 2006 Feb;110(2):235-42
pubmed: 16238546
Clin Pharmacokinet. 2008;47(8):515-31
pubmed: 18611061
Pharmacol Rep. 2008 Sep-Oct;60(5):623-31
pubmed: 19066408
Vasc Health Risk Manag. 2009;5(1):453-63
pubmed: 19475781
Curr Hypertens Rep. 2009 Dec;11(6):456-62
pubmed: 19895758
Nat Rev Cardiol. 2010 Aug;7(8):431-41
pubmed: 20567239
Biotechnol Appl Biochem. 2011 Sep-Oct;58(5):353-62
pubmed: 21995538
J Control Release. 2012 Jul 20;161(2):505-22
pubmed: 22353619
Med Sci Monit. 2013 Jun 12;19:451-7
pubmed: 23756824
Hypertension. 2014 Apr;63(4):878-85
pubmed: 24243703
Mater Sci Eng C Mater Biol Appl. 2014 Feb 1;35:153-63
pubmed: 24411363
J Am Heart Assoc. 2014 Jan 28;3(1):e000606
pubmed: 24473199
J Renin Angiotensin Aldosterone Syst. 2015 Jun;16(2):284-91
pubmed: 25070349
Biotechnol Adv. 2015 Nov 1;33(6 Pt 3):1370-9
pubmed: 25636971
Clin Exp Pharmacol Physiol. 2016 Apr;43(4):450-8
pubmed: 26804705
Artif Cells Nanomed Biotechnol. 2017 Mar;45(2):185-192
pubmed: 26923861
Curr Drug Targets. 2017;18(11):1269-1280
pubmed: 27400970
Sheng Li Xue Bao. 2016 Oct 25;68(5):684-690
pubmed: 27778035
Drug Deliv. 2017 Nov;24(1):358-369
pubmed: 28165823
Cochrane Database Syst Rev. 2017 Apr 05;4:CD007066
pubmed: 28379619
J Appl Toxicol. 2017 Dec;37(12):1359-1369
pubmed: 28383141
J Clin Med. 2017 Jun 09;6(6):
pubmed: 28598381
PLoS One. 2017 Jul 10;12(7):e0180712
pubmed: 28700686
Cochrane Database Syst Rev. 2017 Aug 16;8:CD008276
pubmed: 28813123
Eur J Heart Fail. 2018 Jan;20(1):136-147
pubmed: 28948656
Drug Res (Stuttg). 2018 Mar;68(3):139-145
pubmed: 28977812
Am J Physiol Heart Circ Physiol. 2018 Feb 1;314(2):H278-H284
pubmed: 29101176
Am J Prev Med. 2017 Dec;53(6S2):S131-S142
pubmed: 29153114
Oncotarget. 2017 Jul 19;8(51):89364-89374
pubmed: 29179525
Life Sci. 2018 Oct 1;210:55-64
pubmed: 30170073
Curr Hypertens Rep. 2019 Apr 25;21(6):44
pubmed: 31025117
J Lab Clin Med. 1971 Dec;78(6):957-62
pubmed: 5131859
Br J Pharmacol. 1997 Feb;120(3):399-404
pubmed: 9031742