RESULTS: No significant difference in plasma propranolol (mean +/- SEM) levels was seen between races six hours after the last dose (Malays, 59.7 +/- 8.8 ng/ml, Indians, 67.6 +/- 19.3 ng/ml, Chinese, 58.4 +/- 7.9 ng/ml). Chinese were least sensitive to the bradycardic and hypotensive effects of propranolol at rest and exercise. Indians and Malays had significant reduction of supine systolic blood pressure with propranolol but not Chinese. Comparison of percentage reductions of systolic blood pressure at supine, sitting and exercise by repeated measure analysis showed the Malays to have significantly higher change compared to the Chinese (p = 0.022). Similarly, comparison of percentage reductions of heart rate at supine, sitting and exercise by repeated measure analysis showed the Malays to have significantly higher change compared to the Chinese (p = 0.040). Average change in potassium concentrations at peak exercise and recovery showed the Indians to have significantly higher increase in potassium levels with propranolol compared to the Malays (p = 0.038). However, no significant interethnic difference was seen in the reduction of glucose levels at rest, peak exercise or recovery. Also, no significant interethnic difference was seen in reduction of FEV1 values.
CONCLUSION: We, therefore, conclude that ethnic differences in response to blockade of beta-receptors exist among racial groups in Malaysia. These differences were seen at similar plasma drug levels between races suggesting ethnic differences in drug sensitivity, rather than differences in drug disposition.
Methods: Successive extractions of V. pubescens leaf were carried out to produce petroleum ether (VPPE), chloroform (VPCE), methanol (VPME), and water (VPWE) extracts. Spontaneously hypertensive rats (SHRs) received a daily oral administration of the extracts (500 mg/kg/day; n = 6) or verapamil (15 mg/kg/day; n = 6) for 2 weeks, while the systolic and diastolic blood pressures were measured using non-invasive tail-cuff method. Vasorelaxation assays of the extracts were later conducted using phenylephrine (PE, 1 μM) pre-contracted aortic ring preparation. Mechanisms of vasorelaxation by the most potent fraction were studied using vasorelaxation assays with selected blockers/inhibitors. GC-MS was conducted to determine the active compounds.
Results: VPPE elicited the most significant diminution in systolic and diastolic blood pressure of treated SHRs and produced the most significant vasorelaxation in the aortic rings. Vasorelaxant effects of F2-VPPE were significantly reduced in endothelium-denuded aortic rings by glibenclamide (1 μM), whereas calcium chloride and PE-induced contractions were significantly suppressed. Endothelium removal of the aortic rings or incubation with indomethacin (10 μM), atropine (1 μM), methylene blue (10 μM), propranolol (1μM) and L-NAME (10 μM) did not significantly alter F2-VPPE-induced vasorelaxation. Seven compounds were identified using GC-MS, including spathulenol.
Conclusion: F2-VPPE exerted its endothelium-independent vasorelaxation by inhibition of vascular smooth muscle contraction induced by extracellular Ca+2 influx through trans-membrane Ca+2 channels and/or Ca+2 release from intracellular stores, and by activation of KATP channels. The vasorelaxation effects of V. pubescens could be mediated by the compound, spathulenol.