THE CATECHOLAMINE–β‐ADRENORECEPTOR–cAMP SYSTEM AND PREDICTION OF CARDIOVASCULAR EVENTS IN HYPERTENSION

Abstract

Although the importance of elevated circulating plasma catecholamines on cardiac structural and functional remodelling of hypertension is well documented, it is unclear whether the catecholamine-beta-adrenoreceptor (beta AR)-cAMP system can predict different cardiovascular events. 2. A total of 601 identified hypertensive patients with baseline and follow-up plasma levels of noradrenaline (NA) and adrenaline (Adr), lymphocyte beta AR density (B(max)) and intra-lymphocyte cAMP levels in peripheral blood (last examination 60+/-26 months apart) were followed up for an additional 24+/-12 months. 3. After the last follow up, a composite end-point of cardiovascular death, non-fatal myocardial infarction (MI) and stroke occurred in 139 patients (23.1%). In Cox analyses, adjusting for other standard factors as well as treatment effect, NA (hazard ratio 1.22; 95% confidence interval (CI) 1.17-1.28; P=0.0008), Adr (hazard ratio 1.53; 95% CI 1.18-2.00; P=0.002), beta AR (hazard ratio 1.12; 95% CI 1.06-1.17; P=0.007) and cAMP (hazard ratio 1.15; 95% CI 1.09-1.21; P=0.005) separately predicted cardiovascular mortality. Noradrenaline, Adr, beta AR and intra-lymphocyte cAMP separately predicted fatal/non-fatal MI; NA and Adr predicted fatal/non-fatal stroke, whereas B(max) and intra-lymphocyte cAMP levels were not a significant predictor of fatal/non-fatal stroke. When stratifying the study population by NA or Adr (median 4 nmol/L), B(max) (median 600 fmol/10(7) cells) and cAMP (median 5.0 pmol/mg protein) above and below the median values in both parameters categories, patients above the median had composite cardiovascular end-point (all P<0.001) and high cardiovascular death (all P<0.01, log-rank test). 4. These results suggest that plasma NA and Adr are significant predictors of cardiovascular mortality, MI and stroke. The B(max) and intra-lymphocyte cAMP levels are significant predictors of cardiovascular mortality and MI, but not stroke.

Effect of the α2C-adrenoreceptor deletion322–325 variant on sympathetic activity and cardiovascular measures in healthy subjects

“…Nonetheless, venous norepinephrine concentrations have been used widely as an indirect marker of global sympathetic tone. They are correlated with more specific markers of sympathetic activity such as muscle sympathetic nerve activity (MSNA) at rest [43] and increase similarly after a reduction in blood pressure [44,45], have strong heritability [4], and in longitudinal studies predict cardiovascular morbidity in both healthy subjects [46] and patients with hypertension [47] or congestive heart failure [48,49]. Additionally, we studied subjects at rest, thus minimizing the confounding effect of changes in forearm norepinephrine release and of large differences in catecholamine clearance secondary to altered blood flow.…”

Molecular Mechanisms Underlying β-Adrenergic Receptor-Mediated Cross-Talk between Sympathetic Neurons and Immune Cells

“…In addition to GRK2, immune cells also express GRKs 3, 5, and 6 [ 68 , 69 , 70 ], but these GRKs are less well studied than GRK2. Down-regulation and desensitization of the β 2 -AR is observed in many diseases where net SNS firing rate (activity) is chronically elevated and robust/chronic inflammation ensues, including hypertension [ 71 ], sepsis [ 72 , 73 , 74 ], rheumatoid arthritis (RA) [ 75 , 76 , 77 ], and asthma [ 78 , 79 , 80 ]. For hypertension, changes in lymphocyte β 2 -AR density and poorer responsiveness are significant predictors of cardiovascular mortality and myocardial infarction [ 71 ].…”

Common biomarkers of oxidative stress do not reflect cardiovascular dys/function in rats

“…Coronary heart disease accounts for more than 40% of cardiovascular deaths and its most serious form, acute myocardial infarction (AMI), is the principal cause of chronic heart failure 1 . Elevated catecholamines are known risk factors for a cardiovascular event and the synthetic catecholamine, isoprenaline has been used for about a half a century for inducing AMI and subsequent heart failure in small laboratory animals [7][8][9][10] . In our previous study, we found in a very small number of animals some correlations among various parameters in healthy and AMIinduced animals 10 .…”