{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:47:15Z","timestamp":1790272035497,"version":"4.1.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[1997,7]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>It is well established that the antihypertensive drug clonidine acts through specific imidazoline receptors in the brain and kidney to increase diuresis, natriuresis, and kaliuresis. We have previously shown that the effects of clonidine are associated with elevated plasma atrial natriuretic peptide (ANP). Similar to clonidine, ST-91, a clonidine analogue that does not cross the blood-brain barrier, evokes renal responses that are also associated with elevated plasma ANP. The mechanisms of ANP increase elicited by these imidazoline drugs are unclear. Since ANP is primarily released from the cardiac atria, we investigated the direct effect of the imidazoline drugs on ANP release by incubating left and right atrial sections with 10<jats:sup>\u22126<\/jats:sup>mol\/L ST-91 in the presence and absence of efaroxan, a selective imidazoline I<jats:sub>1<\/jats:sub>receptor antagonist, for 30 minutes at 37\u00b0C. ST-91 significantly stimulated ANP release, and the effect was inhibited by 10<jats:sup>\u22126<\/jats:sup>mol\/L efaroxan. Further studies using heart perfusion with the imidazoline drugs with and without antagonists over 30 minutes revealed that both clonidine and ST-91 gradually stimulated ANP release. Also, perfusion with these compounds resulted in a gradual decrease in heart rate, but bradycardia was significant only with clonidine. The effects of ST-91 were inhibited by 10<jats:sup>\u22126<\/jats:sup>mol\/L efaroxan and to a lesser extent by 10<jats:sup>\u22126<\/jats:sup>mol\/L yohimbine, implying that the actions of ST-91 were mainly mediated by I<jats:sub>1<\/jats:sub>receptors. On the other hand, the actions of clonidine were inhibited by 10<jats:sup>\u22125<\/jats:sup>mol\/L efaroxan and by 10<jats:sup>\u22126<\/jats:sup>mol\/L yohimbine, an \u03b1<jats:sub>2<\/jats:sub>-adrenoceptor antagonist, which may suggest that the actions of clonidine were preferentially mediated by \u03b1<jats:sub>2<\/jats:sub>-adrenoceptors in the heart. These results indicate that the peripheral actions of clonidine are probably mediated by \u03b1<jats:sub>2<\/jats:sub>and imidazoline receptors and may involve direct stimulation of ANP release by the cardiac atria\u2014an effect that may account for the increase in plasma ANP levels and diuresis and natriuresis observed in vivo after administration of clonidine and its analogues.<\/jats:p>","DOI":"10.1161\/01.hyp.30.1.83","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"83-87","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Clonidine and ST-91 May Activate Imidazoline Binding Sites in the Heart to Release Atrial Natriuretic Peptide"],"prefix":"10.1161","volume":"30","author":[{"given":"Suhayla","family":"Mukaddam-Daher","sequence":"first","affiliation":[{"name":"From the Laboratory of Cardiovascular Biochemistry, Research Center, Hotel-Dieu Hospital, Montreal, and Pharmacology Department, Faculty of Medicine, University of Montreal (C.L.) (Quebec, Canada)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Lambert","sequence":"additional","affiliation":[{"name":"From the Laboratory of Cardiovascular Biochemistry, Research Center, Hotel-Dieu Hospital, Montreal, and Pharmacology Department, Faculty of Medicine, University of Montreal (C.L.) (Quebec, Canada)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolanta","family":"Gutkowska","sequence":"additional","affiliation":[{"name":"From the Laboratory of Cardiovascular Biochemistry, Research Center, Hotel-Dieu Hospital, Montreal, and Pharmacology Department, Faculty of Medicine, University of Montreal (C.L.) (Quebec, Canada)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","first-page":"39","volume":"81","year":"1987","unstructured":"Kobinger W. Central alpha-adrenergic systems as targets for hypotensive drugs. 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