This study used a precise noninvasive method in normotensive humans to determine the effects of sympathetic activation on arterial compliance. A recently developed, high-resolution echo-tracking system capable of measuring systolic/diastolic variations of arterial diameter was coupled to a Finapres system and used to calculate instantaneous systolic/diastolic pressure-diameter and compliance-pressure curves for a muscular medium-sized artery, the radial artery. Two standardized tests of sympathetic system activation, a cold pressor test (2 min) and a mental stress test (2 min of mental arithmetic), were performed at an interval of 8 days in random order in nine healthy volunteers [30 +/- 9 (SD) yr]. Radial arterial parameters were recorded every 30 s for 9 min, which included 2 min of cold pressor test or mental stress test. During both tests, radial arterial mean diameter did not change despite t he increase in mean arterial pressure (P < 0.001); stroke change in diameter decreased (P < 0.01), whereas pulse pressure increased (P < 0.01). Arterial compliance, calculated for the instantaneous level of mean arterial pressure, decreased significantly (P < 0.01). Compliance (C) calculated at 100 mmHg (C100) was arbitrarily chosen as a reference point for comparing compliance among the different periods of the test. C100 decreased significant (P < 0.05) during both tests (from 2.93 +/- 1.27 to 2.04 +/- 0.94 and from 3.29 +/- 1.73 to 2.63 +/- 1.55 mm2.mmHg-1.10(-3) during mental stress and the cold pressor test, respectively). These results indicate that sympathetic activation is able to decrease radial arterial compliance in healthy subjects. The reduction in arterial compliance probably resulted from complex interactions between changes in distending blood pressure and changes in radial arterial smooth muscle tone.

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hyperpolarising factor. EETs are synthesised from arachidonic acids by cytochrome P450 enzymes, and soluble epoxide hydrolase (SEH) inhibition may up-regulate EETs. EETs signaling may be implicated in cardiovascular risk groups. The effects of two agonists in stimulating EETs release were compared, and the best agonist was chosen to investigate this pathway in cardiovascular patient groups, and to confirm target engagement in a first in human clinical trial of a novel SEH inhibitor. Methods: Healthy volunteers (12 male, 12 female) underwent 4 forearm venous occlusion plethysmography studies to compare the effects of intraarterial bradykinin and acetylcholine co-infused with saline, fluconazole (cytochrome P450 inhibitor), L-monomethylarginine (nitric oxide synthase inhibitor) plus aspirin (cyclo-oxygenase inhibitor) (LNMMA+ASA), or with all three inhibitors (Triple). Data were analysed by repeated measures analysis of variance. MeanAESEM are presented. Results: Fluconazole had no effect on basal tone (pZ0.25). Bradykinin and acetylcholine both caused dose related vasodilatation (p<0.0001 vs. p<0.001). Fluconazole inhibited bradykinin-induced flow, but not acetylcholine (p<0.0001 vs. pZ0.86). LNMMA+ASA inhibited bradykinin and acetylcholine induced vasodilatation (p<0.0001 vs. p<0.0001). There was no additive effect with triple inhibition. At top agonist doses, fluconazole inhibited bradykinin-induced flow, but not acetylcholine (-18.84AE5.08% vs. 3.36AE9.07%; pZ0.01). LNMMA+ASA inhibited bradykinin and acetylcholine induced flow (-35.74AE7.57% vs. -32.78AE10.60% pZ0.74). There were no gender differences. Conclusions: Basal tone is not dependent on EETs signaling. Bradykinininduced flow is EETs dependent, therefore bradykinin was chosen to probe EETs in cardiovascular patient groups.