The effects of repeated delivery of angiotensin II AT(1) receptor antisense on distinct vasoactive systems in Ren-2 transgenic rats: young vs. adult animals
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22399098
DOI
10.1038/hr.2012.29
PII: hr201229
Knihovny.cz E-resources
- MeSH
- Antihypertensive Agents therapeutic use MeSH
- Oligonucleotides, Antisense therapeutic use MeSH
- Heterozygote MeSH
- Homozygote MeSH
- Hypertension therapy MeSH
- Cardiomegaly drug therapy physiopathology MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Nitric Oxide physiology MeSH
- Rats, Transgenic MeSH
- Receptor, Angiotensin, Type 1 genetics metabolism MeSH
- Renin-Angiotensin System drug effects physiology MeSH
- Aging genetics physiology MeSH
- Sympathetic Nervous System drug effects physiopathology MeSH
- Vasoconstriction drug effects physiology MeSH
- Age Factors MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Agtr1a protein, rat MeSH Browser
- Antihypertensive Agents MeSH
- Oligonucleotides, Antisense MeSH
- Nitric Oxide MeSH
- Receptor, Angiotensin, Type 1 MeSH
Although Ren-2 transgenic rat (TGR) is defined as a model of angiotensin II-dependent hypertension, we studied whether the renin-angiotensin system (RAS) is really the main contributor to blood pressure (BP) elevation in hetero- and homozygous TGRs. Moreover, we examined whether repeated antisense (AS) therapy against AT(1) receptors would have a similar effect on the BP and the contribution of the principle vasoconstrictor/vasodilator systems to BP regulation in young and adult TGRs. From the age of 30 (young) and 100 (adult) days, rats were injected with AS for 40 days in 10-day intervals. After 10 and 40 days of AS therapy, the basal BP and acute BP responses to the sequential blockade of the RAS, sympathetic nervous (SNS) and nitric oxide systems were determined in conscious rats. The RAS system was the major system maintaining elevated BP in young homozygous animals, whereas there was an increasing contribution of the SNS in heterozygous TGR with age. The AS therapy in the young TGR had a transient BP-lowering effect that was associated with reduced cardiac hypertrophy; the AS therapy was most effective in young homozygous TGR, causing a substantial reduction of angiotensin-dependent vasoconstriction. In heterozygous rats, AS therapy at earlier stages was related to an inhibition of sympathetic vasoconstriction, whereas to RAS inhibition in established hypertension. In conclusion, repeated AS therapy had transient antihypertensive effects exclusively in young TGR. The contribution of the RAS to BP maintenance is highly important only in homozygous TGRs, whereas it is surpassed by SNS in heterozygous TGR.
References provided by Crossref.org
Altered Balance between Vasoconstrictor and Vasodilator Systems in Experimental Hypertension
Empagliflozin Is Not Renoprotective in Non-Diabetic Rat Models of Chronic Kidney Disease
