Selective antihypertensive action of moxonidine is mediated mainly by I1-imidazoline receptors in the rostral ventrolateral medulla
| Autor: | Musa A. Haxhiu, S. G. Schafer, Paul Ernsberger, Ismail A. Dreshaj |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Agonist
medicine.medical_specialty Microinjections medicine.drug_class Receptors Drug Alpha (ethology) Imidazoline receptor Blood Pressure In Vitro Techniques Binding Competitive Clonidine chemistry.chemical_compound Radioligand Assay Heart Rate Internal medicine Rats Inbred SHR medicine Animals Adrenergic alpha-Antagonists Antihypertensive Agents Benzofurans Pharmacology Medulla Oblongata Moxonidine Imidazoles Affinity Labels Blood Pressure Determination Rostral ventrolateral medulla Benzazepines Efaroxan Rats Disease Models Animal Endocrinology chemistry Mechanism of action Hypertension Alpha-2 adrenergic receptor Cattle Imidazoline Receptors medicine.symptom Blood Gas Analysis Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | Journal of cardiovascular pharmacology. 24 |
| ISSN: | 0160-2446 |
| Popis: | The rostral ventrolateral medulla (RVLM) is the primary region maintaining vasomotor tone, and a site of action for central antihypertensive agents. In vitro [125I]p-iodoclonidine binding studies showed that moxonidine was selective for I1-imidazoline over alpha 2-adrenergic receptors in the RVLM. We identified efaroxan and SK&F 86466 as selective I1- and alpha 2-antagonists, respectively. We tested moxonidine's action within the RVLM of spontaneously hypertensive rats (SHRs) on I1-imidazoline or alpha 2-adrenergic receptors, and determined whether the RVLM mediates the action of systemic moxonidine. SHRs were anesthetized, paralyzed, and ventilated and the RVLM was localized by testing for a pressor response to 2 nmol glutamate. To test whether I1 or alpha 2 mediates hypotensive effects of moxonidine, the I1/alpha 2 antagonist efaroxan (4 nmol) or the alpha 2-blocker SK&F 86466 (10 nmol) was administered 15 min before 4 nmol moxonidine. Efaroxan elevated blood pressure and abolished the action of moxonidine, whereas alpha 2-blockade with SK&F 86466 slightly lowered blood pressure and only partially attenuated moxonidine's effect. The depressor effect of intravenous moxonidine (40 micrograms/kg) was reversed within 10 min by microinjection of 10 nmol efaroxan into the RVLM. Prior bilateral microinjections of efaroxan (10 nmol in 80 nl/site) into the RVLM prevented the hypotensive action of moxonidine given i.v. (40 micrograms/kg). Pharmacokinetic studies showed that at the peak vasodepressor response (8 min post-injection), [3H]moxonidine spread less than 1 mm from the injection site. Moxonidine is a centrally acting antihypertensive with a selective action on I1-imidazoline receptors in RVLM. |
| Databáze: | OpenAIRE |
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