Vascular beta-adrenergic receptor system is dysfunctional after myocardial infarction.

Abstract

We identified abnormalities in the vascular beta-adrenergic receptor (beta-AR) signaling pathway in heart failure after myocardial infarction (MI). To examine these abnormalities, we measured beta-AR-mediated hemodynamics, vascular reactivity, and the vascular beta-AR molecular signaling components in rats with heart failure after MI. Six weeks after MI, these rats had an increased left ventricular (LV) end-diastolic pressure, decreased LV systolic pressure, and decreased rate of LV pressure change (dP/dt). LV dP/dt responses to isoproterenol were shifted downward, although the responses for systemic vascular resistance were shifted upward in heart failure rats (P < 0.05). Isoproterenol- and IBMX-induced vasorelaxations were blunted in heart failure rats (P < 0.05) with no change in the forskolin-mediated vasorelaxation. These changes were associated with the following alterations in beta-AR signaling (P < 0.05): decreases in beta-AR density (aorta: 58.7 +/- 6.0 vs. 35.7 +/- 1.9 fmol/mg membrane protein; carotid: 29.6 +/- 5.6 vs. 18.0 +/- 3.9 fmol/mg membrane protein, n = 5), increases in G protein-coupled receptor kinase activity levels (relative phosphorimage counts of 191 +/- 39 vs. 259 +/- 26 in the aorta and 115 +/- 30 vs. 202 +/- 7 in the carotid artery, n = 5), and decreases in cGMP and cAMP in the carotid artery (0.85 +/- 0.10 vs. 0.31 +/- 0.06 pmol/mg protein and 2.3 +/- 0.3 vs. 1.2 +/- 0.1 pmol/mg protein, n = 5) with no change in Galpha(s) or Galpha(i )in the aorta. Thus in heart failure there are abnormalities in the vascular beta-AR system that are similar to those seen in the myocardium. This suggests a common neurohormonal mechanism and raises the possibility that treatment in heart failure focused on the myocardium may also affect the vasculature.

• Authors: M A Gaballa, A Eckhart, W J Koch, S Goldman
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 280 Issue 3 Pg. H1129-35 (Mar 2001) ISSN: 0363-6135 [Print] United States
• PMID: 11179056 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adrenergic beta-Agonists
• Receptors, Adrenergic, beta
• Colforsin
• Cyclic AMP
• Aurora Kinases
• Protein Serine-Threonine Kinases
• GTP-Binding Proteins
• Cyclic GMP
• Isoproterenol
• 1-Methyl-3-isobutylxanthine

Topics

• 1-Methyl-3-isobutylxanthine (pharmacology)
• Adrenergic beta-Agonists (pharmacology)
• Animals
• Aorta (metabolism, physiopathology)
• Aurora Kinases
• Blood Pressure
• Carotid Arteries (metabolism, physiopathology)
• Colforsin (pharmacology)
• Coronary Vessels (metabolism, physiopathology)
• Cyclic AMP (metabolism)
• Cyclic GMP (metabolism)
• GTP-Binding Proteins (metabolism)
• Heart Failure (metabolism, physiopathology)
• In Vitro Techniques
• Isoproterenol (pharmacology)
• Ligation
• Muscle, Smooth, Vascular (metabolism, physiopathology)
• Myocardial Infarction (metabolism, physiopathology)
• Protein Serine-Threonine Kinases (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Adrenergic, beta (physiology)
• Signal Transduction (physiology)
• Ventricular Pressure