title: 20-Hydroxyeicosatetraenoic acid contributes to the inhibition of K+ channel activity and vasoconstrictor response to angiotensin II in rat renal microvessels.
abstract: The present study examined whether 20-hydroxyeicosatetraenoic acid (HETE) contributes to the vasoconstrictor effect of angiotensin II (ANG II) in renal microvessels by preventing activation of the large conductance Ca(2+)-activated K(+) channel (KCa) in vascular smooth muscle (VSM) cells. ANG II increased the production of 20-HETE in rat renal microvessels. This response was attenuated by the 20-HETE synthesis inhibitors, 17-ODYA and HET0016, a phospholipase A2 inhibitor AACOF3, and the AT1 receptor blocker, Losartan, but not by the AT2 receptor blocker, PD123319. ANG II (10(-11) to 10(-6) M) dose-dependently decreased the diameter of renal microvessels by 41 ± 5%. This effect was blocked by 17-ODYA. ANG II (10(-7) M) did not alter KCa channel activity recorded from cell-attached patches on renal VSM cells under control conditions. However, it did reduce the NPo of the KCa channel by 93.4 ± 3.1% after the channels were activated by increasing intracellular calcium levels with ionomycin. The inhibitory effect of ANG II on KCa channel activity in the presence of ionomycin was attenuated by 17-ODYA, AACOF3, and the phospholipase C (PLC) inhibitor U-73122. ANG II induced a peak followed by a steady-state increase in intracellular calcium concentration in renal VSM cells. 17-ODYA (10(-5) M) had no effect on the peak response, but it blocked the steady-state increase. These results indicate that ANG II stimulates the formation of 20-HETE in rat renal microvessels via the AT1 receptor activation and that 20-HETE contributes to the vasoconstrictor response to ANG II by blocking activation of KCa channel and facilitating calcium entry.
authors: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
authors: Fan
authors: F
authors: Fan
authors: Cheng-Wen
authors: CW
authors: Sun
authors: Kristopher G
authors: KG
authors: Maier
authors: Jan M
authors: JM
authors: Williams
authors: Malikarjuna R
authors: MR
authors: Pabbidi
authors: Sean P
authors: SP
authors: Didion
authors: John R
authors: JR
authors: Falck
authors: Jialong
authors: J
authors: Zhuo
authors: Richard J
authors: RJ
authors: Roman
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015870:Gene Expression; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D055806:Microvessels / Q000187:drug effects* / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D054467:Phospholipases A2 / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D015759:Ionomycin; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D054467:Phospholipases A2; D010738:Type C Phospholipases; D002118:Calcium