| First Author | Gamella-Pozuelo L | Year | 2017 |
| Journal | Biochim Biophys Acta | Volume | 1863 |
| Issue | 1 | Pages | 113-120 |
| PubMed ID | 27771508 | Mgi Jnum | J:256827 |
| Mgi Id | MGI:6104563 | Doi | 10.1016/j.bbadis.2016.10.014 |
| Citation | Gamella-Pozuelo L, et al. (2017) Tyrosine hydroxylase haploinsufficiency prevents age-associated arterial pressure elevation and increases half-life in mice. Biochim Biophys Acta 1863(1):113-120 |
| abstractText | Catecholamines are essential for the maintenance of physiological homeostasis under basal and stress conditions. We aim to determine the impact of deletion of a single allele of the tyrosine hydroxylase (Th) gene might have on aging arterial pressure and life-span. We found that Th haploinsufficiency prevents age-associated increase of arterial pressure (AP) in mature adult mice, and it results in the extension of the half-life of Th-heterozygous (TH-HET) mice respect to their wild-type (WT) littermates. Heart performance was similar in both genotypes. To further investigate the lack of increase in AP with age in TH-HET mice, we measured the AP response to intra-peritoneal administration of substances involved in AP regulation. The response to acetylcholine and the basal sympathetic tone were similar in both genotypes, while norepinephrine had a greater pressor effect in TH-HET mice, which correlated with altered adrenoreceptor expression in blood vessels and the heart. Furthermore, sympatho-adrenomedular response to stress was attenuated in TH-HET mice. Plasma catecholamine levels and urine glucose increased markedly in WT but not in TH-HET mice after stress. Our results showed that TH-HET mice are resistant to age-associated hypertension, present a reduction in the sympathetic response to stress and display an extended half-life. |
