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Atherosclerosis. 1998 Jan;136(1):153-61.
Psychosocial stress causes endothelial injury in cynomolgus monkeys via beta1-adrenoceptor activation.

Skantze HB, Kaplan J, Pettersson K, Manuck S, Blomqvist N, Kyes R, Williams K, Bondjers G.

The Wallenberg Laboratory, Sahlgren's Hospital, Gothenburg, Sweden.

Current evidence links psychosocial factors to exacerbation of diet-induced atherosclerosis in monkeys via activation of the sympathetic nervous system. However, it is uncertain whether these factors can potentiate initial lesion formation, and do so even in the absence of dietary provocation, and whether any such effects can be prevented by beta-adrenergic blockade. As endothelial injury has been considered an initiating event in atherogenesis, we studied the effect of psychosocial stress on endothelial integrity in 48 adult male cynomolgus monkeys (Macaca fascicularis). All animals were housed in 12 social groups of four monkeys each for 11 weeks. The monkeys in half of the groups were exposed to a socially unstable ('stressed') condition for 72 h and received saline (n = 8), a lipophilic beta1-blocker (metoprolol, 0.30 mg/kg per h; n = 8), or hydrophillic beta1-blocker (atenolol, 0.15 mg/kg per h; n = 8). The remaining six social groups were assigned to the socially stable (non-stressed) condition; for 72 h these animals all remained in their social groups and were similarly treated with saline (n = 8), metoprolol (n = 8), or atenolol (n = 8). The frequency of IgG-positive (injured) endothelial cells was estimated on en face (Hautchen) preparations from the thoracic aorta and coronary arteries. Psychosocial stress caused a significant increase in the number of injured endothelial cells in the circumostial areas of the descending thoracic aorta in the placebo group (0.3 vs. 0.8%, P < 0.02), an effect that had not been demonstrated previously. Moreover, beta-blockade significantly (P < 0.01) inhibited the stress effect, with no differences between the two beta-blocking agents. The number of injured endothelial cells in the non-branched portions of the aorta and coronary arteries were low and indistinguishable among groups; irregularities in the size and location of branching points in the coronary arteries precluded analysis of these sites. This study demonstrated that psychosocial stress induces endothelial injury, and that this effect is mediated via beta1-adrenoceptor activation.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9544742&dopt=Abstract




Eur J Clin Pharmacol. 1984;26(4):425-7.
Lack of influence of beta adrenergic blockade on serum potassium during an infusion of potassium.

Smith SR, Kendall MJ, Ryder C, Laugher S.

The extent to which the serum potassium rose in a group of six healthy volunteers during an intra-venous infusion of potassium was identical following pretreatment with placebo, low or high dose propranolol and low or high dose metoprolol. Thus in this acute study, we were unable to demonstrate any influence of either selective or non-selective beta adrenergic blockade upon potassium uptake mechanisms. This is in contrast to the effects of beta blockers on potassium reuptake rates noted after exercise and during cardiac surgery.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6329768&dopt=Abstract




J Am Coll Cardiol. 1994 Dec;24(7):1762-8.
Angiotensin-converting enzyme inhibition and beta-adrenoceptor blockade regress established ventricular remodeling in a canine model of discrete myocardial damage.

McDonald KM, Rector T, Carlyle PF, Francis GS, Cohn JN.

Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.

OBJECTIVES. This study was designed to assess the effect of angiotensin-converting enzyme inhibition and beta-adrenoreceptor blockade on established ventricular remodeling. BACKGROUND. Angiotensin-converting enzyme inhibitor therapy attenuates the development of ventricular remodeling when given shortly after myocardial infarction. However, regression of established ventricular remodeling after infarction has received little attention. METHODS. The relative effects of angiotensin-converting enzyme inhibitor therapy and beta-adrenoceptor blockade on established ventricular remodeling were assessed in a canine model characterized by increased left ventricular mass and chamber dilation as a result of localized myocardial necrosis produced by transmyocardial direct current shock. Dogs were randomly assigned to 3 months of therapy with captopril (25 mg twice daily, n = 7) or metoprolol (100 mg twice daily, n = 7) or to a control group with no intervention (n = 6), 11 +/- 4 (mean +/- SD) months after acute myocardial damage. RESULTS. Compared with the control group, dogs in both the captopril and metoprolol groups had reduced left ventricular mass as measured by magnetic resonance imaging (-8.1 +/- 3.8 vs. 1.7 +/- 2.8 g, p = 0.003 and -9.6 +/- 5.6 vs. 1.7 +/- 2.8 g, p = 0.001), respectively. Captopril and metoprolol also produced a reduction in left ventricular end-diastolic volume (-7.6 +/- 6.0 and -6.0 +/- 5.8 ml, respectively) compared with the control value (-1.6 +/- 3.8 ml) (p = 0.14 [NS]). Both agents reduced mean arterial pressure but had disparate effects on pulmonary wedge pressure and right atrial pressure. There was no significant correlation between change in ventricular mass or volume and change in any measured hemodynamic or neurohormonal variable. CONCLUSIONS. These data suggest that pharmacologic intervention with angiotensin-converting enzyme inhibition or beta-adrenoceptor blockade can result in regression of established ventricular remodeling. The mechanism of this response will require further study, but these data did not support a close association between regression of remodeling and hemodynamic unloading of the ventricle or systemic neuroendocrine factors.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7963126&dopt=Abstract













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