Contribution of nitric oxide and prostaglandins to reactive hyperemia in human forearm.
We investigated the separate and combined contributions of nitric oxide (NO) and vasodilating prostaglandins as mediators of reactive hyperemia in the human forearm. Forearm blood flow (FBF) was measured with venous occlusion plethysmography after 5 min of ischemia. In one protocol (n = 12), measurements were made before and after intra-arterial administration of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) to one forearm. In a separate protocol (n = 7), measurements were made before and after systemic administration of the cyclooxygenase inhibitor ibuprofen and again after L-NMMA. L-NMMA reduced baseline FBF at rest (2.7 +/- 0.4 to 1.6 +/- 0.2 ml.100 ml-1.min-1; P < 0.05) and had a modest effect on peak forearm vascular conductance and flow (forearm vascular conductance = 31.1 +/- 3.1 vs. 25.7 +/- 2.5 ml.min-1.100 ml forearm-1.100 mmHg of perfusion pressure-1.min-1, P < 0.05; FBF = 26.6 +/- 2.9 vs. 22.8 +/- 2.6 ml.100 ml-1.min-1, P = 0.055). Total excess flow above baseline during reactive hyperemia was unaffected by L-NMMA (14.3 +/- 3.0 vs. 13.1 +/- 2.4 ml/100 ml; P < 0.05). Ibuprofen did not change FBF at rest, reduced peak FBF from 27.6 +/- 1.9 to 20.3 +/- 2.7 ml.100 ml-1.min-1 (P < 0.05), but had no effect on total excess flow above baseline, Infusion of L-NMMA after ibuprofen reduced FBF at rest by 40%, had no effect on peak flow, but reduced total excess flow above baseline from 12.0 +/- 2.5 to 7.6 +/- 1.3 ml/100 ml (P < 0.05). These date demonstrate that NO synthase inhibition has a modest effect on peak vasodilation during reactive hyperemia but plays a minimal role later. Prostaglandins appear to be important determinants of peak flow. The effects of NO synthase inhibition during reactive hyperemia may also be potentiated by concurrent cyclooxygenase inhibition.
Department of Anesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
K A
KA
Engelke
J R
JR
Halliwill
D N
DN
Proctor
N M
NM
Dietz
M J
MJ
Joyner
D000293:Adolescent; D000328:Adult; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply* / Q000502:physiology; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology*; D007052:Ibuprofen / Q000494:pharmacology; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D007052:Ibuprofen