Related Experiment Video
Updated: Aug 16, 2026
A Simple and Efficient Method for In Vivo Cardiac-specific Gene Manipulation by Intramyocardial Injection in Mice
Published on: April 16, 2018
Cardiovascular effects of newly discovered peptide intermedin/adrenomedullin 2
Chun-Shui Pan1, Jing-Hui Yang, Da-Yong Cai
1Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, PR China.
Abstract:
Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CGRP). The present study aimed to investigate the cardiovascular effects of IMDs (IMD1-47 and IMD8-47) in rats. Intravenous administration of 150 nmol IMDs continuously decreased mean arterial pressure and inhibited cardiac function. Administration with IMDs decreased left ventricular end-systolic pressure (LVESP) and maximal rate of left-ventricle pressure development (+/-LVdp/dt(max)), and elevated left ventricular end-diastolic pressure (LVEDP). Changes with IMD1-47 treatment were close to that with IMD8-47 (P>0.05). Perfusion of isolated rat hearts in vitro with IMD8-47 (10(-8) and 10(-7)mol/L) resulted in lower LVSP, by 40 and 56% (P<0.01); lower +LVdp/dt (max), by 33 and 47% (P<0.01); lower -LVdp/dt(max), by 25 and 39% (P<0.01); but higher coronary perfusion flow (CPF), by 25% (P<0.05) and 33% (P<0.01), respectively, than controls. However, both IMD8-47 and IMD1-47 (from 10(-13) to 10(-7)mol/L) relaxed preconstricted aortic rings in a dose-dependent manner. Intravenous administration of IMD1-47 and IMD8-47 (10(-7)mol/L) in vivo increased the cyclic adenosine monophosphate (cAMP) content by 68 and 150% (both P<0.01), respectively, in myocardia and 320 and 281% (both P<0.01), respectively, in aortas, compared with controls. Perfusion of isolated hearts with IMD1-47 and IMD8-47 (10(-7)mol/L) enhanced cAMP content by 24% (P<0.05) and 73% (P<0.01), respectively, compared with controls. IMDs inhibited 3H-Leucine incorporation in cardiomyocytes in a concentration-dependent manner. IMD1-47 and IMD8-47 (10(-7) and 10(-8)mol/L) decreased 3H-Leucine incorporation by 12-25% (P<0.01) and 14-18% (P<0.01), respectively. IMD mRNA was detected in cultured neonatal cardiomyocytes and isoproterenol-induced hypertrophic myocardia but not normal myocardia of adult rats. These results suggest that IMD might be a regulatory factor for cardiovascular function and myocardial hypertrophy as a cardiovascular active peptide.
Insights
Intermedin (IMD) peptides reduced blood pressure and cardiac function in rats. IMDs also relaxed aortic rings and affected cyclic adenosine monophosphate (cAMP) levels, suggesting a role in cardiovascular regulation.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Molecular Biology
Background:
- Intermedin (IMD) is a novel peptide within the calcitonin/calcitonin gene-related peptide (CGRP) family.
- The cardiovascular effects and regulatory roles of IMD peptides require further investigation.
Purpose of the Study:
- To investigate the cardiovascular effects of IMD1-47 and IMD8-47 in rat models.
- To explore the impact of IMDs on cardiac function, vascular tone, and intracellular signaling pathways.
Main Methods:
- Intravenous administration of IMDs in rats to assess hemodynamic parameters.
- In vitro perfusion of isolated rat hearts and aortic ring assays.
- Measurement of cyclic adenosine monophosphate (cAMP) levels and protein synthesis markers (3H-Leucine incorporation).
- Detection of IMD mRNA in cardiac tissues.
Main Results:
- IMDs significantly decreased mean arterial pressure, cardiac contractility (LVESP, +/-LVdp/dt(max)), and elevated LVEDP.
- IMDs induced vasodilation in aortic rings and increased coronary perfusion flow in isolated hearts.
- IMDs elevated cAMP levels in cardiac and aortic tissues and inhibited protein synthesis in cardiomyocytes.
- IMD mRNA was detected in neonatal and hypertrophic cardiomyocytes.
Conclusions:
- IMD peptides exert significant cardiovascular effects, including hypotension and altered cardiac function.
- IMDs modulate vascular tone and intracellular cAMP signaling, indicating a role in cardiovascular regulation.
- IMD may function as a regulatory factor in cardiovascular function and myocardial hypertrophy.
Related Concept Videos
01:30Adrenergic Agonists: Therapeutic Uses
Emergency and Intensive Care Unit (ICU) applications: Pressor agents increase blood pressure, heart rate, and contractility in shock and organ failure situations. Dopamine can induce vasodilation and stimulate adrenoceptors. Endogenous catecholamines are effective in treating cardiogenic shock. α2-agonists like clonidine can reverse anesthesia-induced hypertension.
Allergies and anaphylaxis:...
01:30Adrenergic Agonists: Direct-Acting Agents
These agents can be classified...
01:31Adrenergic Receptors: ɑ Subtype
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
01:25Adrenergic Agonists: Indirect-Acting Agents
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
01:27Adrenergic Antagonists: Pharmacological Actions of β-Receptor Blockers
01:26Adrenergic Receptors: β Subtype
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors have equal affinities for...