PubMed Health⌕ Search

PubMed · 14732736

Decrease in hypothalamic gamma adducin in rat models of hypertension.

Abstract

We have previously shown that a decrease in hypothalamic gamma adducin (gamma-adducin) is associated with hypertension in the spontaneously hypertensive rat (SHR). In view of many inherent issues with SHR, our objective in the present study was to provide proof of this concept with the use of 2 nongenetic rat models of hypertension. Subcutaneous angiotensin II (Ang II) infusion for 2 weeks (55 ng/kg per day) resulted in an increase in blood pressure (BP) of 18 mm Hg. This was associated with a 70% decrease in hypothalamic gamma-adducin. Concomitant administration of losartan attenuated the development of hypertension and a decrease in gamma-adducin. Deoxycorticosterone acetate salt-induced hypertension also caused a 70% decrease in hypothalamic gamma-adducin. Finally, neuronal cultures from neonatal rat brains were incubated with 100 nmol/L Ang II for 4 hours to mimic the in vivo Ang II infusion rat model. This chronic incubation with Ang II resulted in a 60% decrease in the neuronal gamma-adducin. Taken together, these observations strengthen our hypothesis that a decrease in hypothalamic gamma-adducin is linked to hypertension.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Hong Yang, Phyllis Y Reaves, Michael J Katovich, Mohan K Raizada. 2004-01-19. Decrease in hypothalamic gamma adducin in rat models of hypertension.. https://doi.org/10.1161/01.hyp.0000113045.12850.cd

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Angiotensin II-induced ERK1/ERK2 activation and protein synthesis are redox-dependent in glomerular mesangial cells.

Angiotensin II (Ang II) stimulates hypertrophy of glomerular mesangial cells. The signalling mechanism by which Ang II exerts this effect is not precisely known. Downstream potential targets of Ang II are the extracellular-signal-regulated kinases 1 and 2 (ERK1/ERK2). We demonstrate that Ang II activates ERK1/ERK2 via the AT1 receptor. Arachidonic acid (AA) mimics the action of Ang II on ERK1/ERK2 and phospholipase A2 inhibitors blocked Ang II-induced ERK1/ERK2 activation. The antioxidant N-acetylcysteine as well as the NAD(P)H oxidase inhibitors diphenylene iodonium and phenylarsine oxide abolished both Ang II- and AA-induced ERK1/ERK2 activation. Moreover, dominant-negative Rac1 (N17Rac1) blocks activation of ERK1/ERK2 in response to Ang II and AA, whereas constitutively active Rac1 resulted in an increase in ERK1/ERK2 activity. Antisense oligonucleotides for Nox4 NAD(P)H oxidase significantly reduce activation of ERK1/ERK2 by Ang II and AA. We also show that protein synthesis in response to Ang II and AA is inhibited by N17Rac1 or MEK (mitogen-activated protein kinase/ERK kinase) inhibitor. These results demonstrate that Ang II stimulates ERK1/ERK2 by AA and Nox4-derived reactive oxygen species, suggesting that these molecules act as downstream signal transducers of Ang II in the signalling pathway linking the Ang II receptor AT1 to ERK1/ERK2 activation. This pathway involving AA, Rac1, Nox4, reactive oxygen species and ERK1/ERK2 may play an important role in Ang II-induced mesangial cell hypertrophy.

Angiotensin II↗

Effect of saponin and filipin on antagonist binding to AT 1 receptors in intact cells.

In the present study, [ 3H ]-candesartan binding experiments were performed on intact Chinese Hamster Ovary cells transfected with the human AT1 receptor (CHO-AT1 cells). Cells were pre-treated with 0.01mg/ml saponin or filipin. Both pre-treatments resulted in an increased dissociation rate and decreased affinity of the insurmountable non-peptide antagonist [3H ]-candesartan. A similar decrease in affinity was observed for the peptide antagonist Sar1-Ile8 angiotensin II and for other non-peptide antagonists, irrespectively of their degree of insurmountability. A similar discrepancy in [ 3H ]-candesartan binding was earlier observed when comparing intact CHO-AT1 cells and membrane preparations thereof. This similarity is further highlighted by the observations that saponin or filipin no longer affect [ 3H ]-candesartan binding to CHO-AT1 cell membranes and that both agents permeabilise the CHO-AT1 cells. This suggests that the intracellular composition and/or organisation of living cells play an active role with regard to antagonist-AT1 receptor interactions.

Angiotensin II↗

Peri-implantation undernutrition programs blunted angiotensin II evoked baroreflex responses in young adult sheep.

An adverse environment around conception and implantation influences later fetal growth and development to term in humans and sheep. Indeed, preimplantation undernutrition of rats elevated the systolic blood pressure of the resultant adult offspring. In this study, adult cardiovascular function is examined in a slower growing, non-litter-bearing species after peri-implantation undernutrition. Eight ewes were fed to 50% equivalent food intake of 12 control ewes from 1 to 30 days (term approximately 147 days) only. Following consumption of an adequate diet to term, natural lambing, and then weaning, resting cardiovascular status and baroreflex function were examined in the resultant young adult offspring. Birth weight and postnatal growth to 1 year of age were unaffected by early undernutrition; however, nutrient-restricted sheep had increased pulse pressure, a reduced rate pressure product, and a leftward shift in their baroreflex function curve. Baroreflex sensitivity during angiotensin II infusion was also blunted in early nutrient-restricted sheep but the tachycardia following a reduction in central blood pressure appeared potentiated, relative to controls. The data suggest that peri-implantation undernutrition may program long-term cardiovascular dysfunction that ultimately increases the risk of hypertension later in life. An increase in regional angiotensin II activity during this critical early phase of development is a likely candidate mechanism for the effects observed. The data have broad implications for the health outcome of those offspring from mothers who were poorly nourished during early, often unknown pregnancy and for embryos artificially manipulated because of infertility treatment.

Angiotensin II↗