Heterogeneity of endothelium-dependent vasodilation in pressurized cerebral and small mesenteric resistance arteries of the rat.
We compared endothelial responses to calcium-mobilizing agents in mesenteric and cerebral resistance arteries of the rat. Middle cerebral and small mesenteric arteries were mounted in a pressure myograph, and myogenic responses were recorded. The effects of acetylcholine (ACh), bradykinin, substance P, histamine, A23187, cyclopiazonic acid (CPA), and sodium nitroprusside were investigated in both arteries with myogenic tone in the absence and presence of nitric oxide synthase and cyclooxygenase inhibitors. The effects of raised potassium, K(+) channel blockers, and arachidonic metabolism inhibition were examined on the nitric oxide (NO) synthase/cyclooxygenase inhibitor-resistant dilation induced by ACh and CPA. Cerebral arteries display a high level of myogenic reactivity compared with mesenteric arteries. In cerebral arteries, only bradykinin and substance P induced endothelium-dependent dilation. The observed dilation was solely related to the activation of the NO pathway. However, in mesenteric arteries, all of the vasoactive agents induced endothelium-dependent dilation. A combination of NO, cyclooxygenase-derived prostanoids, and a factor with endothelium-derived hyperpolarizing factor-like properties was responsible for the observed vasodilation. NO and cyclooxygenase derivatives were able to compensate for each other in the CPA-induced endothelium-dependent vasodilation when one of the two pathways was blocked. Moreover, small Ca(2+)-activated K(+) channels and a combination of both large and small Ca(2+)-activated K(+) channels were implicated in the endothelium-derived hyperpolarizing factor-like component of dilation to ACh and CPA, respectively. Finally, the results suggest that the pathway by which agonists raise intracellular calcium concentration may determine the nature of the endothelial secretory product.
Vancouver Vascular Biology Research Centre, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
G J
GJ
Lagaud
P L
PL
Skarsgard
I
I
Laher
C
C
van Breemen
D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D015221:Potassium Channels / Q000819:agonists; D024681:Potassium Channels, Calcium-Activated; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; C067410:endothelium-dependent hyperpolarization factor; D019001:Nitric Oxide Synthase; D002118:Calcium