Abstract
Hinokitiol, a natural monoterpenoid, has been shown previously to possess a potent vasodilating activity in vitro in both control and hypertensive aortae. Here, the antihypertensive and cardioprotective effects of an intravenous hinokitiol injection were fully investigated in angiotensin II-induced hypertensive emergency in rats. Hinokitiol intravenous injection was prepared in the form of self-nanoemulsifying drug delivery system. Rat's arterial and ventricular hemodynamics were measured in real-time recordings in addition to surface electrocardiogram while slow injection of cumulative doses of hinokitiol or vehicle as well as time control. Hinokitiol at dose 10 mg/kg showed a considerable reduction in the raised systolic blood pressure (30 mmHg) within only 30 min. The decrease in blood pressure seems to be mediated through a reduction in peripheral resistance, as appears from the decreases in diastolic pressure, dicrotic notch pressure, and pulse pressure. In addition, hinokitiol injection reduced heart load due to the decrease in heart rate, increases in cycle duration (particularly the non-ejection duration) and diastolic duration, and decreases in end-diastolic pressure. An effect most likely mediated via prolongation of ventricular repolarization as appears from the increases in PR, QTc, and JT intervals. However, acute intravenous injection of hinokitiol neither affected the baroreflex sensitivity nor sodium/potassium balance. In conclusion, acute hinokitiol intravenous injection markedly reduced severe hypertension in rats. This effect seems to be mediated through decreasing peripheral resistance and decreasing cardiac load, suggesting that it is an effective treatment in hypertensive emergencies after clinical evaluation.