Thyroid heart disease in the elderly
Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich in Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Tachycardia is frequently present in hyperthyroidism. Initially, this was felt to be associated with an altered responsiveness to adrenergic input. Other data support a direct effect of thyroid hormone on pacemaker activity through the sinoatrial (SA) node (44). An increased venous return, secondary to a decreased systemic vascular resistance, activated renin–angiotensin–aldosterone system, and subsequently increased blood volume contribute to the increase in preload reported in hyperthyroid states (5,6,43,45–47). Although these findings contribute to the augmented cardiac output associated with hyperthyroidism, cardiac contractility is increased in cardiac myocytes removed from peripheral effects (15,16). Systemic vascular resistance is decreased directly by thyroid hormone’s action on vascular smooth muscle cells as evidenced by invasive measurement after coronary artery bypass surgery (17). This may be mediated through thyroid hormone-stimulated increased activity of adrenomedullin—a potent vasodilatory peptide (7). Afterload is reduced in hyperthyroid patients as a result of direct arterial smooth muscle relaxation, which leads to an improvement in stroke volume and subsequently cardiac output. A comprehensive review evaluated steady and pulsatile components of afterload and hypothesized that pulsatile components of arterial load actually compensate for the reduction in systemic vascular resistance noted in hyperthyroidism. These data cast doubt on the simplified notion of a single factor such as systemic vascular resistance controlling the observed decrease in ventricular afterload in the hyperthyroid patient (43).
Pathogenesis of gestational diabetes mellitus
Moshe Hod, Lois G. Jovanovic, Gian Carlo Di Renzo, Alberto de Leiva, Oded Langer in Textbook of Diabetes and Pregnancy, 2018
Adrenomedullin is a newly discovered hypotensive peptide involved in the insulin regulatory system, and it may play a role in modifying diabetes in pregnancy. Di Iorio et al.46 studied its correlation to GDM. Adrenomedullin concentrations were measured in maternal and fetal plasma and in amniotic fluid in diabetic and nondiabetic pregnancies. Overall amniotic fluid concentration was higher in the pregnant diabetic women (type 1 or GDM), but there was no difference between the group in maternal and fetal plasma levels. These findings suggest that placental adrenomedullin production is upregulated in diabetic pregnancy and that it may be important to prevent excessive vasoconstriction of placental vessels.
New treatments for hypertension
H. Gavras in The Year in Hypertension 2004, 2004
The pathogenesis and development of cardiovascular disease involve a variety of physiological components including: neurohormonal and haemodynamic factors; the sympathetic and parasympathetic nervous systems; the renin-angiotensin- aldosterone system (RAAS); the endothelin system; the natriuretic peptide system; nitric oxide (NO); and adrenomedullin. Although these neurohumoral systems are essential in vascular homeostasis, they become maladaptive in disease states such as hypertension, coronary heart disease, and heart failure. The development of drugs that enhance the action of some peptides, such as natriuretic peptides, bradykinin, and adrenomedullin, may represent an important therapeutic advance for patients with cardiovascular disease. These peptides may attenuate vasoconstriction and sodium retention as well as retard cardiac and vascular hypertrophy and remodelling, thus ameliorating some of the pathophysiological abnormalities contributing to hypertension and cardiovascular disease. Research in this field has led to the development of dual inhibitors of neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE), sometimes called 'vasopeptidase inhibitors' |1|. By simultaneously inhibiting the RAAS and potentiating the action of natriuretic peptides and the kinin system, as well as adrenomedullin, vasopeptidase inhibitors reduce vasoconstriction, enhance vasodilation, and improve local blood flow. Within the blood vessel wall, this leads to a reduction of vasoconstrictor and proliferative mediators such as angiotensin II, and to increased local levels of bradykinin and, in turn, NO and natriuretic peptides as well as adrenomedullin (Fig. 11.1).
Heart failure risk estimation based on novel biomarkers
Published in Expert Review of Molecular Diagnostics, 2021
Feven Ataklte, Ramachandran S. Vasan
Adrenomedullin (ADM) is an amino acid peptide that is synthesized by endothelial and vascular smooth cells. Its concentration is increased in circulation during left ventricular volume overload [19,20]. Mid-regional pro-adrenomedullin (MR-proADM) is a more stable form of ADM that has a longer plasma half-life [18,19]. MR-proADM is expressed in many tissues including the heart, kidney and blood vessels. It exerts its biological effect as a vasodilator, positive inotrope, diuretic, and natriuretic role. High circulating levels of MR-proADM have been observed in patients with HF and hypertension, and also in non-cardiac diseases, e.g. sepsis and kidney failure [19]. The non-cardiac conditions associated with elevated levels of MR-proADM and HF share common underlying mechanisms of vascular leakage and systemic or pulmonary edema, suggesting ADM’s specific role in vascular congestion [20].
The effect of swimming training on adrenomedullin levels, oxidative stress variables, and gastrocnemius muscle contractile properties in hypertensive rats
Published in Clinical and Experimental Hypertension, 2021
ECE KOC Yildirim, Zahide Dedeoglu, Mehmet Kaya, Aykut G. Uner
Aerobic exercise training can reduce blood pressure via improving vascular stiffness and endothelial function (42) and altering the balance between vasodilation- and vasoconstriction-related compounds such as NO (19), prostacyclin, and thromboxane (43). As a product of cardiovascular system, adrenomedullin may also have played important roles in the regulation of blood pressure. Even though the studies on the relationship between exercise and adrenomedullin levels are contradictory, it seems like adrenomedullin responses depending on the severity of cardiovascular diseases (44,45) and the type of the exercise as demonstrated by the fact that dynamic, static, and maximal exercises affect adrenomedullin levels differently (46-48). The results of several studies (49,50) indicate that the reduction in the levels of ADM may play an important role in the pathogenesis of L-NAME-induced hypertension. However, our correlation analysis indicates that there is no relationship with ADM levels and SP and DP. The studies by Sugo et al. (4, 50) may explain the absence of ADM response to exercise. They reported that the synthesis of ADM in vascular endothelial cells was regulated by gene expression and its secretion occurred in constitutive manner. Our exercise protocol may not have been long enough to stimulate the synthesis and secretion of ADM by gene expression.
Newer approaches and novel drugs for inhalational therapy for pulmonary arterial hypertension
Published in Expert Opinion on Drug Delivery, 2020
Ali Keshavarz, Hossam Kadry, Ahmed Alobaida, Fakhrul Ahsan
Adrenomedullin has been implicated as a key player in cardiovascular events and has vasodilatory and antiproliferative properties, resulting in a beneficial effect on PAH treatment [203]. Harada-Shiba et al. reported on the use of PEG-based cationic micelles (polyplex nanomicelles) for intratracheal, nonviral gene transfer to the lung of rats with monocrotaline-induced PAH. Polyplex nanomicelles were formulated with a therapeutic plasmid bearing the human adrenomedullin gene. Intratracheal administration of PEG-polyplex nanomicelles showed remarkable therapeutic efficacy with PAH animal models, as evidenced by significantly decreasing the right ventricular pressure three days after administration, which was confirmed by a notable increase of pulmonary human adrenomedullin mRNA levels [204].