Abstract
To investigate lisinopril effect on the contribution of nitric oxide (NO) and K(Ca) channels to acetylcholine (ACh)-induced relaxation in isolated mesenteric arteries of spontaneously hypertensive rats (SHRs). Third branch mesenteric arteries isolated from lisinopril treated SHR rats (20 mg/kg/day for ten weeks, SHR-T) or untreated (SHR-UT) or normotensive WKY rats were mounted on tension myograph and ACh concentration-response curves were obtained. Westernblotting of eNOS and K(Ca) channels was performed. ACh-induced relaxations were similar in all groups while L-NMMA and indomethacin caused significant rightward shift only in SHR-T group. Apamin and TRAM-34 (SK(Ca) and IK(Ca) channels blockers, respectively) significantly attenuated ACh-induced maximal relaxation by similar magnitude in vessels from all three groups. In the presence of L-NMMA, indomethacin, apamin and TRAM-34 further attenuated ACh-induced relaxation only in SHR-T. Furthermore, lisinopril treatment increased expression of eNOS, SK(Ca) and BK(Ca) proteins. Lisinopril treatment increased expression of eNOS, SK(Ca), BK(Ca) channel proteins and increased the contribution of NO to ACh-mediated relaxation. This increased role of NO was apparent only when EDHF component was blocked by inhibiting SK(Ca) and IK(Ca) channels. Such may suggest that in mesenteric arteries, non-EDHF component functions act as a reserve system to provide compensatory vasodilatation if (and when) hyperpolarization that is mediated by SK(Ca) and IK(Ca) channels is reduced.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin-Converting Enzyme Inhibitors / pharmacology*
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Animals
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Antihypertensive Agents / pharmacology*
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Hypertension / drug therapy*
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Hypertension / metabolism
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Hypertension / physiopathology
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Intermediate-Conductance Calcium-Activated Potassium Channels / drug effects
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Intermediate-Conductance Calcium-Activated Potassium Channels / metabolism
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Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / drug effects
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Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / metabolism
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Lisinopril / pharmacology*
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Male
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Mesenteric Arteries / drug effects*
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Mesenteric Arteries / metabolism
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Mesenteric Arteries / physiopathology
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Nitric Oxide / metabolism*
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Nitric Oxide Synthase Type III / antagonists & inhibitors
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Nitric Oxide Synthase Type III / metabolism
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Potassium Channel Blockers / pharmacology
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Potassium Channels, Calcium-Activated / drug effects*
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Potassium Channels, Calcium-Activated / metabolism
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Rats, Inbred SHR
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Rats, Inbred WKY
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Signal Transduction / drug effects
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Small-Conductance Calcium-Activated Potassium Channels / drug effects
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Small-Conductance Calcium-Activated Potassium Channels / metabolism
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Vasodilation / drug effects*
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Vasodilator Agents / pharmacology*
Substances
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Angiotensin-Converting Enzyme Inhibitors
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Antihypertensive Agents
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Intermediate-Conductance Calcium-Activated Potassium Channels
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Kcnma1 protein, rat
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Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
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Potassium Channel Blockers
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Potassium Channels, Calcium-Activated
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Small-Conductance Calcium-Activated Potassium Channels
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Vasodilator Agents
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Nitric Oxide
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Lisinopril
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Nitric Oxide Synthase Type III
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Nos3 protein, rat