Cardiovascular effects of a labdenic diterpene isolated from Moldenhawera nutans in conscious, spontaneously hypertensive rats

摘要

Context: The labdenic diterpene labd-8(17)-en-15-oic acid (labd-8) isolated from a methanolic extract of Moldenhawera nutans Queiroz & Alkin (Leguminosae) has hypotensive and tachycardiac properties in normotensive rats. A part of the hypotensive effect was due to a reduction in the sympathetic nerve drive to vessels, an event admittedly enhanced in spontaneously hypertensive rats (SHRs).Objectives: We assessed whether the cardiovascular effects induced by labd-8 could be enhanced in SHRs.Materials and methods: For in vivo experiments, arterial and venous catheters were implanted under anesthesia for blood pressure recording and drug administration, respectively. For in vitro experiments, thoracic aorta rings were suspended in organ baths containing warm (37?°C) perfusion medium that was continuously bubbled with carbogen.Results: Intravenous injection of labd-8 (1, 3, 5, and 10?mg/kg) induced similar dose-dependent hypotension and tachycardia in both SHRs and Wistar–Kyoto rats (WKY). In SHRs, only the tachycardia response to labd-8 was significantly reduced by pretreatment with methylatropine or propranolol. However, both cardiovascular effects of labd-8 were reduced by hexamethonium while remained unchanged by l -NAME. In isolated aortic preparations from SHRs, labd-8 (1–1000?μg/mL) relaxed potassium-induced contractions with an IC₅₀ (geometric mean [95% confidence interval]) value (536.5 [441.0–631.9] μg/mL) significantly greater than that (157.6 [99.1–250.5] μg/mL) obtained in preparations from WKY rats.Conclusion: In SHRs, the hypotension induced by labd-8 is associated with a reflex tachycardia and seems mediated partly through withdrawal of sympathetic vasomotor tone and partly through an active vasorelaxation. Its magnitude was not enhanced when compared with WKY rats likely because of impaired vasorelaxant effects of labd-8 in preparations from SHRs.