Engidawork, Ephrem (PhD)Tolessa, TesfayeGetiye, Yohannes2018-06-272023-11-062018-06-272023-11-062014-03http://etd.aau.edu.et/handle/123456789/4274Being the most important modifiable risk factor for stroke, renal, vascular and heart diseases; hypertension is still one of the leading causes of disability, morbidity and mortality among the populace worldwide. Consequently, the continued search for alternative antihypertensive agents of natural origin, with fewer side effects but greater effectiveness, necessitated evaluation of Calpurnia aurea for possible antihypertensive potential. In this study, the antihypertensive property of hydro-alcoholic seed extract of Calpurnia aurea was assessed using in vivo and ex vivo techniques. The in vivo antihypertensive efficacy of the crude extracts was evaluated in normotensive and 2K1C rat model of hypertension. The crude extract caused a significant fall in systolic blood pressure (SBP), diastolic blood pressure (DBP)and mean arterial blood pressure (MABP) at the doses of 15, 30 and 45 mg/kg in normotensive anaesthetized rats (p < 0.05, p < 0.01, p< 0.001).The effect on DBP was greater than SBP. In the same manner with the normotensive study, the BP fell dose-dependently and significantly in renal hypertensive rats, induced by renal ischemia. The extract produced 15.4% (p< 0.05), 26.9% (p< 0.01), 33.2% (p <0.01) reduction in SBP at the respective doses of 15, 30 and 45 mg/kg. Similar to the normotensive result, higher DBP effect was observed; 15.1% (p< 0.05), 30.2% (p< 0.01), 36.1% (p <0.01) fall from the control value at the above mentioned doses. Regarding MABP; 15.2% (p< 0.05), 28.8% (p <0.01) and 34.9% (p <0.01) reduction was noted with 15 mg/kg, 30 mg/kg and 45 mg/kg doses of the extract, respectively. The extract also caused a dose-dependent relaxation of guinea pig aorta precontracted with KCl (80mM),at a concentration of 5–250 mg/mL, with a maximum relaxation of 92.1±0.72% (p < 0.001) achieved at 250 mg/mL concentration. The relaxation mechanism was found to be independent of the endothelium system, muscarinic iv receptors, histamine receptors, ATP dependent K+ channels, cyclooxygenase enzymes and cGMP/NO pathway. The relaxation may be correlated with the effect on calcium ion channels, as it shifted the Ca2+ dose response curve (p< 0.05, p< 0.01 and p< 0.001) to the right with suppression of the maximum effect by 37.4% (p < 0.001). In conclusion, the findings suggest that the extract had a promising antihypertensive effect most likely caused by dilation of the blood vessels through Ca++ channel blockade, a confirmation for the folkloric use of the plant. Key words: Hypertension, Calpurnia aurea, hydro-alcoholic seed extract, in vivo, ex vivo, antihypertensive, vasorelaxation.enHypertensionCalpurnia aureahydro-alcoholic seed extractThesis