Effects of nonspecific β-adrenergic stimulation and blockade on blood coagulation in hypertension

Abstract

A hypercoagulable state might contribute to increased atherothrombotic risk in hypertension. The sympathetic nervous system is hyperactive in hypertension, and it regulates hemostatic function. We investigated the effect of nonspecific beta-adrenergic stimulation (isoproterenol) and blockade (propranolol) on clotting diathesis in hypertension. Fifteen hypertensive and 21 normotensive subjects underwent isoproterenol infusion in two sequential, fixed-order doses of 20 and then 40 ng. kg(-1). min(-1) for 15 min/dose. Thirteen subjects were double-blind studied after receiving placebo or propranolol (100 mg/day) for 5 days each. In hypertensive subjects, isoproterenol elicited a dose-dependent increase in plasma von Willebrand factor (vWF) antigen [F(2,34) = 5.02; P = 0.032] and a decrease in D-dimer [F(2,34) = 4.57; P = 0.040], whereas soluble tissue factor remained unchanged. Propranolol completely abolished the increase in vWF elicited by isoproterenol [F(1,12) = 10.25; P = 0.008] but had no significant effect on tissue factor and D-dimer. In hypertension, vWF is readily released from endothelial cells by beta-adrenergic stimulation, which might contribute to increased cardiovascular risk. However, beta-adrenergic stimulation alone may not be sufficient to trigger fibrin formation in vivo.

The role of stress hormones in the relationship between resting blood pressure and coagulation activity

“…We mention four limitations of our study. First, even though catecholamine infusion consistently elicited coagulation activation in previous studies [25,26], the significant associations between stress hormones and coagulation factors, as related to MBP, do not prove a causal link in our study. Second, to prevent spurious associations by chance, some investigators would require higher levels of significance than we observed in terms of some associations between stress hormones and coagulation measures.…”

“…Nonetheless, a greater amount of acute norepinephrine release predicted a higher level of acute D-dimer formation. This notion is consistent with early studies showing that catecholamine infusion dosedependently elicited hemostatic changes in plasma within minutes [25,26] consequent to a rapid release of hemostatic molecules from extravascular compartments into the circulation through a b 2 -adrenergic mechanism [15]. Given previous research on greater stress procoagulant reactivity in hypertensives than in normotensives [20,21], the negative association between MBP and the increase of FVIII:C from rest to immediately after stress independent of epinephrine and norepinephrine change was rather unexpected.…”

“…We selected these coagulation measures because we recently found them to be responsive to acute psychosocial stress in a group of healthy and normotensive middle-aged men [24] other than those included in the present study. Granted that stress axes are more active with higher BP [18,19,22] and that sympathetic activation kindles procoagulability in a dose-response manner [24][25][26], we assumed a mechanism by which elevated stress hormones with higher MBP promote greater coagulability at rest, in response to acute stress, and during recovery from stress. The novel aspect of our investigation was therefore to examine in one study whether hormones of both stress axes have a specific effect on different coagulation factors in relation to resting blood pressure level.…”

Regulation of Hemostasis by the Sympathetic Nervous System: Any Contribution to Coronary Artery Disease?

“…Adrenergic infusion and blockade studies in vivo suggest that catecholamines -by stimulating ß2-adrenergic vascular receptors -provoke a rapid release of FVIII, vWF und t-PA stored in the endothelium into the circulation [20,24]. We found that the amount of norepinephrine secretion and the sensitivity of the ß2-adrenergic receptor together explained almost 60% of the variance in thrombin formation with acute mental stress [34].…”

“…Compared to individuals without atherosclerotic diseases, subjects with atherosclerosis appear to experience an even greater and, therefore, potentially harmful shift in the coagulation-fibrinolysis balance toward hypercoagulability following adrenergic infusions [20,24,25].…”