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Mechanisms of endothelial P2Y1- and P2Y2-mediated vasodilatation involve differential [Ca2+]iresponses
- Source :
- American Journal of Physiology-Heart and Circulatory Physiology. 281:H1759-H1766
- Publication Year :
- 2001
- Publisher :
- American Physiological Society, 2001.
-
Abstract
- The present study was designed to evaluate the role of endothelial intracellular Ca2+concentration ([Ca2+]i) in the difference between P2Y1- and P2Y2-mediated vasodilatations in cerebral arteries. Rat middle cerebral arteries were cannulated, pressurized, and luminally perfused. The endothelium was selectively loaded with fura 2, a fluorescent Ca2+indicator, for simultaneous measurement of endothelial [Ca2+]iand diameter. Luminal administration of 2-methylthioadenosine 5′-triphosphate (2-MeS-ATP), an endothelial P2Y1agonist, resulted in purely nitric oxide (NO)-dependent dilation and [Ca2+]iincreases up to ∼300 nM (resting [Ca2+]i= 145 nM). UTP, an endothelial P2Y2agonist, resulted in dilations that were both endothelium-derived hyperpolarizing factor (EDHF)- and NO-dependent with [Ca2+]iincreases to >400 nM. In the presence of NG-nitro-l-arginine-indomethacin to inhibit NO synthase and cyclooxygenase, UTP resulted in an EDHF-dependent dilation alone. The [Ca2+]ithreshold for NO-dependent dilation was 220 vs. 340 nM for EDHF. In summary, the differences in the mechanism of vasodilatation resulting from stimulation of endothelial P2Y1and P2Y2purinoceptors result in part from differential [Ca2+]iresponses. Consistent with this finding, these studies also demonstrate a higher [Ca2+]ithreshold for EDHF-dependent responses compared with NO.
- Subjects :
- Male
medicine.medical_specialty
Endothelium-derived hyperpolarizing factor
Physiology
Indomethacin
Cerebral arteries
Uridine Triphosphate
Vasodilation
Pharmacology
Nitric Oxide
Nitroarginine
Receptors, Purinergic P2Y2
Biological Factors
Receptors, Purinergic P2Y1
Adenosine Triphosphate
Physiology (medical)
medicine.artery
Internal medicine
medicine
Animals
Cyclooxygenase Inhibitors
Rats, Long-Evans
Enzyme Inhibitors
Receptors, Purinergic P2
Chemistry
Intracellular Membranes
Cerebral Arteries
Thionucleotides
Rats
Endothelial stem cell
Endocrinology
medicine.anatomical_structure
Middle cerebral artery
Circulatory system
Calcium
Endothelium, Vascular
Cardiology and Cardiovascular Medicine
Intracellular
Blood vessel
Subjects
Details
- ISSN :
- 15221539 and 03636135
- Volume :
- 281
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Heart and Circulatory Physiology
- Accession number :
- edsair.doi.dedup.....724224b0a53dbe31eab12dcb581a5bf9
- Full Text :
- https://doi.org/10.1152/ajpheart.2001.281.4.h1759