Acute systemic inflammation impairs endothelium-dependent dilatation in humans.
BACKGROUND
We tested the hypothesis that endothelial dysfunction underlies the association between an acute inflammatory episode and the transiently increased risk of a cardiovascular event by examining the effects of an experimental inflammatory stimulus on endothelium-dependent vasodilation.


RESULTS
Salmonella typhi vaccine was used to generate a systemic inflammatory response in healthy volunteers. In 12 subjects, dilatation of the brachial artery to flow and to sublingual nitroglycerin (NTG) was recorded (conduit vessel response), and in 6 subjects, venous occlusion plethysmography was used to measure forearm blood flow during intrabrachial infusion of the endothelium-dependent dilators acetylcholine (ACh) and bradykinin (BK) and the endothelium-independent dilators NTG and verapamil (resistance vessel response). Responses were assessed 16 hours before and 8 and 32 hours after vaccination. Vaccination resulted in elevations in white cell count and serum levels of interleukin-6 and interleukin-1 receptor antagonist. Eight hours after vaccination, resistance vessel responses to BK (P:=0.0099) and ACh (P:=0.0414) were markedly attenuated, and brachial artery flow-mediated dilatation was depressed. Resistance vessel responses to verapamil and NTG were unchanged, as was the conduit vessel response to NTG. Thirty-two hours after vaccination, resistance vessel responses to BK and ACh had returned to normal.


CONCLUSIONS
S typhi vaccine generates a mild inflammatory reaction associated with temporary but profound dysfunction of the arterial endothelium in both resistance and conduit vessels to both physical and pharmacological dilator stimuli. This finding might explain the association between infection and inflammation and the enhanced risk of an acute cardiovascular event.
Hingorani
A D
AD
Centre for Clinical Pharmacology, University College London, UK. a.hingorani@ucl.ac.uk
Cross
J
J
Kharbanda
R K
RK
Mullen
M J
MJ
Bhagat
K
K
Taylor
M
M
Donald
A E
AE
Palacios
M
M
Griffin
G E
GE
Deanfield
J E
JE
MacAllister
R J
RJ
Vallance
P
P
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000704:Analysis of Variance; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D001783:Blood Flow Velocity; D001916:Brachial Artery; D001920:Bradykinin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005542:Forearm; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D022562:Salmonella Vaccines; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014435:Typhoid Fever / Q000517:prevention & control; D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014700:Verapamil / Q000494:pharmacology
D001428:Bacterial Vaccines; D007375:Interleukin-1; D015850:Interleukin-6; D022562:Salmonella Vaccines; D014409:Tumor Necrosis Factor-alpha; D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated; D014665:Vasodilator Agents; C087350:aroA Salmonella vaccine; D014700:Verapamil; D005996:Nitroglycerin; D000109:Acetylcholine; D001920:Bradykinin