Intermedin in Paraventricular Nucleus Attenuates Sympathoexcitation and Decreases TLR4-Mediated Sympathetic Activation via Adrenomedullin Receptors in Rats with Obesity-Related Hypertension.
Mice with endothelium-specific deficiency of adrenomedullin, the adrenomedullin receptor, or Gαs showed reduced flow-induced eNOS activation and vasodilation and developed hypertension.
Adrenomedullin in the rostral ventrolateral medulla (RVLM) has been shown to increase sympathetic activity whereas the antagonism of its receptors inhibited this autonomic activity lowering blood pressure in conditions of hypertension.
Elevated plasma levels of the vasodilating hormone adrenomedullin (ADM) predict cardiovascular disease and have been associated with hypertension and obesity.
Taken together, postmenopausal rats with hypertension suffered from structural cerebellar changes than rats with only hypertension or estrogen deficiency separately due to augmentation of the increased oxidative stress markers and the proinflammatory cytokines (TNF-α) with down regulation of the anti-inflammatory cytokine (IL-10) and the blood pressure regulator, AM.
These results indicated that IMD via AM receptors in the PVN attenuates SNA and hypertension, and decreases Ang II-induced enhancement of SNA through the inhibition of NADPH oxidase activity and ERK activation.
In the multivariate analysis, boys carrying ADM AG genotype (vs. carriers of ADM GG genotype), ADM AG + AA genotype (vs. carriers of ADM GG genotype) and ADM AG genotype (vs. carriers of ADM GG + AA genotype) had higher odds of having hypertension in codominant, dominant, and overdominant inheritance models.
These changes may constitute a mechanism which contributes to the development of hypertension, and supports the notion that cerebellar AM is involved in the regulation of blood pressure.
The PASP level in neonates with HPH is related to the serum HIF-1α, ET-1 and ADM levels, indicating that hypoxia can increase the level of HIF-1α, which in turn will enhance the expression of downstream target genes ET-1 and ADM, further leading to pulmonary hypertension.
Cerebellar AM, AM binding sites and receptor components are altered during hypertension, suggesting a role for cerebellar AM in blood pressure regulation.
NLR family, pyrin domain containing 6/angiotensin-vasopressin receptor (NLRP6/AVR), and adrenomedullin (ADM) are in close proximity to D11S1318 and D11S1346, respectively; thus we tested single nucleotide polymorphisms (SNPs) within NLRP6/AVR and ADM for their association with hypertension in our Sardinian cohort.
Chronic inhibition of nitric oxide (NO) synthesis is associated with hypertension, myocardial ischemia, oxidative stress and hypertrophy; expression of the vasodilator peptide, adrenomedullin (AM) and its receptors is augmented in cardiomyocytes, indicating that the myocardial AM system may be activated in response to pressure loading and ischemic insult to serve a counter-regulatory, cardio-protective role.
The results suggest that the changes of AM and its receptors in cardiovascular tissue, and the increased response of cardiovascular tissue to AM might importantly impact the pathogenesis of hypertension.
These findings have raised the possibility that decreased expression of adrenomedullin by tumor necrosis factor-alpha may be related to the increased risk of hypertension and other cardiovascular diseases in obese subjects.
Furthermore, transplantation of AM DNA-transduced EPCs markedly ameliorated pulmonary hypertension in MCT rats (39% decrease in pulmonary vascular resistance).
Collectively, these results indicate that human AM gene delivery attenuates hypertension, myocardial infarction, renal injury and cardiovascular remodeling in animal models via cAMP and cGMP signaling pathways.