Vol. 284, Issue 3, H790-H797, March 2003
Prostaglandin modulation of venoconstriction to physiological
stress in normals and heart failure patients
T. Nancy
Dzeka1 and
J. Malcolm O.
Arnold1,2
Departments of 1 Physiology and Pharmacology and
2 Medicine, The University of Western Ontario, and
Lawson Health Research Institute, London, Ontario, Canada
N6A 4G5
Prostaglandins
released from blood vessels modulate vascular tone, and inhibition of
their production during exogenous infusions of catecholamines causes
increased venoconstriction. To determine the influence of prostaglandin
production on venoconstriction during physiological stimuli known to
cause sympathetic activation, and to assess its importance in chronic
heart failure (CHF), we studied 11 normal subjects (62 ± 4 yr)
and 14 patients with CHF (64 ± 2 yr, left ventricular ejection
fraction 23 ± 1%, New York Heart Association classes II and III)
(means ± SE). Dorsal hand vein distension was measured during
mental arithmetic (MA), cold pressor test (CPT), and lower body
negative pressure (LBNP; 
10 and 40 mmHg), with saline infusion in
one hand and local indomethacin (cyclooxygenase inhibitor) infusion (3 µg/min) in the other. Acetylcholine (0.01-1 nmol/min) dilated
veins preconstricted with PGF2
in normals but,
consistent with endothelial dysfunction, barely did so in CHF patients
(P = 0.001). Nonendothelial venodilation to sodium
nitroprusside (0.3-10 nmol/min) was not different between normals
and CHF patients. Resting venous norepinephrine levels were higher in
CHF patients (2,812 ± 420 pmol/l) than normals (1,418 ± 145 pmol/l, P = 0.007). In normals, indomethacin caused increased venoconstriction to MA (from 4.9 ± 1.5 to 19.2 ± 4.5%, P = 0.022) and CPT (from 2.9 ± 3.8 to
17.6 ± 4.2%, P = 0.007). In CHF, indomethacin
caused increased venoconstriction to MA (from 6.6 ± 3.9% to
19.0 ± 4.5%, P = 0.014), CPT (from 9.6 ± 2.1% to 20.1 ± 3.7%, P = 0.001), and 40 mmHg
LBNP (from 10.7 ± 3.0% to 23.2 ± 3.8%, P = 0.041). Control responses for all tests were not different between
normals and CHF patients. The effects of indomethacin on
venoconstriction to MA and CPT were not different between normals
and CHF patients, but venoconstriction to 40 mmHg LBNP was
accentuated in CHF patients (P = 0.036). Inhibition of
prostaglandins by indomethacin significantly enhances hand vein
constriction to physiological stimuli in both normals and CHF patients,
although a differential effect exists for LBNP.
vasoconstriction; sympathetic nervous system; chronic heart
failure
