The hemodynamic basis for the cardiac effects of parathyroid hormone (PTH) and PTH-related protein.

Oginö, Kazuhíde; Burkhoff, Daniel; Bilezikian, John P.

doi:10.1210/endo.136.7.7789328

Cited by 99 publications

(13 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The left ventricle (LV) pressure, LV end-diastolic pressure, LV dP/dt max , LV dP/ dt min , and E max (slope of the end-systolic pressurevolume relation) were measured (14). To estimate the effects of β-adrenergic stimulation, the following agents were used; isoproterenol hydrochloride (TO-KYO CHEMICAL INDUSTRY Co., LTD, Tokyo, Japan), pimobendan (Abcam plc, Cambridge, UK), and dibutyryl cyclic-AMP (Santa Cruz Biotechnology, Inc., Texas) were purchased.…”

Section: Measurement Of Cardiac Function In Isolated Perfused Heartsmentioning

confidence: 99%

Adipose stem cell sheets improved cardiac function in the rat myocardial infarction, but did not alter cardiac contractile responses to β-adrenergic stimulation

et al. 2015

View full text Add to dashboard Cite

Adipose stem cells (ASCs) are a source of regenerative cells available for autologous transplantation to hearts. We compared protective actions of ASC sheets on rat myocardial infarction (MI) in comparison with those of skeletal myoblast cell sheets. Their effects on infarcted hearts were evaluated by biological, histochemical as well as physiological analyses. ASC sheets secreted higher concentrations of angiogenic factors (HGF, VEGF, and bFGF; P < 0.05) under normoxic and hypoxic conditions than those of myoblast cell sheets, associated with reduction of cell apoptosis (P < 0.05). Like myoblast cell sheets, ASC sheets improved cardiac function (P < 0.05) and decreased the plasma level of ANP (P < 0.05) in MI hearts. ASC sheets restored cardiac remodeling characterized by fibrosis, cardiac hypertrophy and impaired angiogenesis (P < 0.05), which was associated with increases in angiogenic factors (P < 0.05). In isolated perfused rat hearts, ASC sheets improved both systolic and diastolic functions, which was comparable to cardiac functions of myoblast cell sheets, while both cell sheets failed to restore cardiac contractile response to either isoproterenol, pimobendan or dibutyryl cAMP. These results indicated that ASC sheets improved cardiac function and remodeling of MI hearts mediated by their paracrine action and this improvement was comparable to those by myoblast cell sheets.

show abstract

Section: Measurement Of Cardiac Function In Isolated Perfused Heartsmentioning

confidence: 99%

Adipose stem cell sheets improved cardiac function in the rat myocardial infarction, but did not alter cardiac contractile responses to β-adrenergic stimulation

et al. 2015

View full text Add to dashboard Cite

show abstract

“…However, the exact role of PHPT in the development of cardiovascular changes, its extent and clinical significance are still controversial (12). Several mechanisms seem to play a role in the association between PHPT and cardiovascular risk: high serum calcium levels (13), increased circulating parathyroid hormone (PTH) levels (14), enhanced activity of the renin -angiotensin system (15) and vascular wall function impairment (16,17). While acute administration of PTH has a vasodilator effect (18), prolonged exposition to exogenous PTH led to increased blood pressure levels in healthy volunteers (19).…”

Section: Introductionmentioning

confidence: 99%

Increased intima-media thickness of the carotid artery wall, normal blood pressure profile and normal left ventricular mass in subjects with primary hyperparathyroidism

Nuzzo

Tauchmanovà

Fonderico

et al. 2002

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: Despite the increasing evidence that primary hyperparathyroidism (PHPT) contributes to greater risk of cardiovascular morbidity and mortality, its exact role in the development of cardiovascular changes and its clinical significance are still controversial. Given the multiple influence of PHPT on the cardiovascular system, this study aimed to assess the effects of PHPT on blood pressure profile, and on features of the heart and arterial vessels in normotensive symptomless patients. Design: Twenty patients (8 males and 12 females) with a median age of 51.5 years (range 44 to 65 years) were evaluated and the results were compared with those of 20 controls matched for age, gender and body mass index. Patients' parathyroid hormone levels ranged from 172 to 454 pg/ml and Ca levels ranged from 11.4 to 13.5 mg/dl. Fasting levels of glucose, insulin, total and high density lipoprotein cholesterol and triglycerides were within the normal range in all subjects recruited. Methods: Twenty-four-hour blood pressure profile, left ventricle (LV) dimension and carotid artery anatomy were investigated, the latter two by ultrasonography. Results: No difference was found between the patients and controls in blood pressure profile, when the following parameters were considered: supine systolic/diastolic pressure, average 24-h systolic, diastolic and mean arterial pressure, day-time mean arterial pressure and fall in nocturnal blood pressure (217% and 2 18% respectively). Heart rate and all parameters of LV mass were similar in patients and controls. The only alteration found in patients was in significantly greater carotid intimal-medial thickness (IMT) ðP , 0:001Þ: Atherosclerotic plaques were more frequent in patients than in controls, with a difference reaching a trend (40% vs 10%, x 2 ¼ 4:8; P ¼ 0:091). Considering that the carotid IMT is considered to be a marker of systemic atherosclerosis, our finding suggests early atherosclerotic changes in PHPT. No correlation was found between the severity and cardiovascular manifestation of PHPT. Conclusions: Vascular changes may occur due to a combination of structural and functional impairments in PHPT patients, likely as a result of altered calcium metabolism and impaired equilibrium of other factors regulating vascular function. Both extent and duration of PHPT can play a relative role in the development of cardiovascular complications. Considering that PHPT is now recognized as a quite common and often symptomless endocrine disorder, the evidence of cardiovascular manifestation in normotensive patients, found by this morphological study, suggests a possible implication for the management of such patients. In this light, screening for abnormalities in cardiovascular system function should be recommended in all PHPT subjects.

show abstract

“…3,6 PTH and PTHrp are devoid of direct effects on ventricular contraction at physiological concentrations in vivo. 7 In the cardiomyocyte, PTH and PTHrp induce hypertrophy acting via an endogenously occurring, yet uncloned, myocardial PTH receptor subtype 8 and therefore contribute to further worsening of heart failure. At physiological concentrations, neither PTH nor PTHrp nor AVP stimulates cAMP generation in cardiomyocytes.…”

mentioning

confidence: 99%

Gene Transfer of Heterologous G Protein–Coupled Receptors to Cardiomyocytes

Laugwitz

Weig

Moretti

et al. 2001

Circulation Research

View full text Add to dashboard Cite

Abstract-In heart failure, reduced cardiac contractility is accompanied by blunted cAMP responses to ␤-adrenergic stimulation. Parathyroid hormone (PTH)-related peptide and arginine vasopressin are released from the myocardium in response to increased wall stress but do not stimulate contractility or adenylyl cyclase at physiological concentrations.To bypass the defective ␤-adrenergic signaling cascade, recombinant P1 PTH/PTH-related peptide receptors (rPTH1-Rs) and V 2 vasopressin receptors (rV 2 -Rs), which are normally not expressed in the myocardium and which are both strongly coupled to adenylyl cyclase, and recombinant ␤ 2 -adrenergic receptors (r␤ 2 -ARs) were overexpressed in cardiomyocytes by viral gene transfer. The capacity of endogenous hormones to increase contractility via the heterologous, recombinant receptors was compared. Whereas V 2 -Rs are uniquely coupled to Gs, PTH1-Rs and ␤ 2 -ARs are also coupled to other G proteins. Gene transfer of rPTH1-Rs or r␤ 2 -ARs to adult cardiomyocytes resulted in maximally increased basal contractility, which could not be further stimulated by adding receptor agonists. Agonists at rPTH1-Rs induced increased cAMP formation and phospholipase C activity. In contrast, healthy or failing rV 2 -Rexpressing cardiomyocytes showed unaltered basal contractility. Their contractility and cAMP formation increased only at agonist exposure, which did not activate phospholipase C. In summary, we found that gene transfer of PTH1-Rs to cardiomyocytes results in constitutive activity of the transgene, as does that of ␤ 2 -ARs. In the absence of receptor agonists, rPTH1-Rs and r␤ 2 -ARs increase basal contractility, coupling to 2 G proteins simultaneously. In contrast, rV 2 -Rs are uniquely coupled to Gs and are not constitutively active, retaining their property to be activated exclusively on agonist stimulation. Therefore, gene transfer of V 2 -Rs might be more suited to test the effects of cAMP-stimulating receptors in heart failure than that of PTH1-Rs or ␤ 2 -ARs. (Circ Res. 2001;88:688-695.)Key Words: gene transfer Ⅲ receptor Ⅲ heart failure C ongestive heart failure is characterized by an increased sympatho-adrenergic drive; a stimulation of the reninangiotensin-aldosterone system; and an augmented release of several peptide hormones, among them atrial natriuretic peptide, arginine vasopressin (AVP), and parathyroid hormone (PTH)-related peptide (PTHrp). 1-3 AVP is released both systemically from the pituitary gland and locally from the myocardium. 2,4 In addition, PTHrp is released from the heart in response to increased wall stress or hypoxia, 5 and PTHrp mRNA has been detected in isolated cardiomyocytes. 3,6 PTH and PTHrp are devoid of direct effects on ventricular contraction at physiological concentrations in vivo. 7 In the cardiomyocyte, PTH and PTHrp induce hypertrophy acting via an endogenously occurring, yet uncloned, myocardial PTH receptor subtype 8 and therefore contribute to further worsening of heart failure. At physiological concentrations, neither PTH nor PT...

show abstract

The hemodynamic basis for the cardiac effects of parathyroid hormone (PTH) and PTH-related protein.

Cited by 99 publications

References 21 publications

<b>Adipose stem cell sheets improved cardiac function in the rat myocardial infarction, but did not alter cardiac contractile responses to β-adrenergic stim</b><b>ulation </b>

<b>Adipose stem cell sheets improved cardiac function in the rat myocardial infarction, but did not alter cardiac contractile responses to β-adrenergic stim</b><b>ulation </b>

Increased intima-media thickness of the carotid artery wall, normal blood pressure profile and normal left ventricular mass in subjects with primary hyperparathyroidism

Gene Transfer of Heterologous G Protein–Coupled Receptors to Cardiomyocytes

Contact Info

Product

Resources

About