Abstract:Abstract-Arterial baroreflex function diminishes with age, but whether cardiopulmonary vagal reflexes are similarly altered with physiological aging has not been fully elucidated. In this study, predominantly cardiac high pressure mechanoreceptor-activated (ramp baroreflex) and cardiopulmonary chemoreceptor-activated (von Bezold-Jarisch reflex) vagal reflexes in conscious, instrumented rats were impaired by 30% to 40% (PϽ0.05) in 24-month-old (nϭ12) compared with 6-month-old rats (nϭ12). To determine whether t… Show more
“…Additional studies in anesthetized canines demonstrated that ANPdependent decreases in monophasic action potential and effective refractory period are due to secondary autonomically mediated effects (33). Another study demonstrated that these vagal reflexes can be activated both by ANP infusion and by inhibiting its degradation by blocking NEP (26). The implication from the Hodgson-Zingman study is that in patients expressing fsANP, these vagal reflexes would be under more prolonged pressure because of the elevated levels of total ANP (wtANP ϩ fsANP), which would eventually lead to early onset atrial fibrillation.…”
The frameshift product (fsANP), but not wild-type ANP (wtANP), was elevated in the serum of affected patients, but the molecular basis for the elevated peptide concentrations was not determined. Here, we measured the ability of fsANP to interact with natriuretic peptide receptors and to be proteolytically degraded. fsANP and wtANP bound and activated human NPR-A and NPR-C similarly, whereas fsANP had a slightly increased efficacy for human NPR-B. Proteolytic susceptibility was addressed with novel bioassays that measure the time required for kidney membranes or purified neutral endopeptidase to abolish ANP-dependent activation of NPR-A. The half-life of fsANP was markedly greater than that of wtANP in both assays. Additional membrane proteolysis studies indicated that wtANP and fsANP are preferentially degraded by neutral endopeptidase and serine peptidases, respectively. These data indicate that the familial ANP mutation associated with atrial fibrillation has only minor effects on natriuretic peptide receptor interactions but markedly modifies peptide proteolysis.
“…Additional studies in anesthetized canines demonstrated that ANPdependent decreases in monophasic action potential and effective refractory period are due to secondary autonomically mediated effects (33). Another study demonstrated that these vagal reflexes can be activated both by ANP infusion and by inhibiting its degradation by blocking NEP (26). The implication from the Hodgson-Zingman study is that in patients expressing fsANP, these vagal reflexes would be under more prolonged pressure because of the elevated levels of total ANP (wtANP ϩ fsANP), which would eventually lead to early onset atrial fibrillation.…”
The frameshift product (fsANP), but not wild-type ANP (wtANP), was elevated in the serum of affected patients, but the molecular basis for the elevated peptide concentrations was not determined. Here, we measured the ability of fsANP to interact with natriuretic peptide receptors and to be proteolytically degraded. fsANP and wtANP bound and activated human NPR-A and NPR-C similarly, whereas fsANP had a slightly increased efficacy for human NPR-B. Proteolytic susceptibility was addressed with novel bioassays that measure the time required for kidney membranes or purified neutral endopeptidase to abolish ANP-dependent activation of NPR-A. The half-life of fsANP was markedly greater than that of wtANP in both assays. Additional membrane proteolysis studies indicated that wtANP and fsANP are preferentially degraded by neutral endopeptidase and serine peptidases, respectively. These data indicate that the familial ANP mutation associated with atrial fibrillation has only minor effects on natriuretic peptide receptor interactions but markedly modifies peptide proteolysis.
“…In animals, increased levels of NPs or chronic inhibition of NEP are able to prevent the progression of cardiac aging (158,159). Similarly, in humans, simultaneous inhibition of NEP and Ang-II type-1 receptor (AT1R) with LCZ-696 (which is composed by Valsartan and Sacubitril) has shown to reduce significantly mortality and hospitalization in patients with HF (160).…”
Worldwide increase in life expectancy is a major contributor to the epidemic of chronic degenerative diseases. Aging, indeed, simultaneously affects multiple organ systems, and it has been hypothesized that systemic alterations in regulators of tissue physiology may regulate this process. Cardiac aging itself is a major risk factor for cardiovascular diseases and, because of the intimate relationship with the brain, may contribute to increase the risk of neurodegenerative disorders. Blood-borne factors may play a major role in this complex and still elusive process. A number of studies, mainly based on the revival of parabiosis, a surgical technique very popular during the 70s of the 20 th century to study the effect of a shared circulation in two animals, have indeed shown the potential that humoral factors can control the aging process in different tissues. In this article we review the role of circulating factors in cardiovascular aging. A better understanding of these mechanisms may provide new insights in the aging process and provide novel therapeutic opportunities for chronic age-related disorders.
“…Этот механизм, по-видимому, имеет отношение к феномену относительной или абсолютной (парадоксальной при гипотензии) брадикардии и проявляется даже при низких (негипотензивных) концентрациях ANP [7,77,84]. Важно, что введение ANP или увеличение его концентрации в циркулирующей крови, благодаря лекарственному воздействию (ингибитором нейтральной эндопептидазы), приводит к увеличению чувствительности кардиопульмональных вагусных рефлексов, включая рефлекс Бецольда-Яриша [320,321]. В то же время ANP обладает свойствами антагониста симпатической нервной системы, способного оказывать подавляющие эффекты на всех уровнях барорефлекторной дуги.…”
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.