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Hinokitiol for hypertensive emergencies: Effects on peripheral resistance, cardiac load, baroreflex sensitivity, and electrolytes balance


      Background and purpose: We previously showed that hinokitiol, a natural monoterpenoid, produces a significant vasodilating action in vitro in both control and hypertensive aortae. Here, the antihypertensive and cardioprotective effects of an i.v. hinokitiol formulation were fully investigated in angiotensin II-induced hypertensive crisis in rats. Experimental Approach: Hinokitiol i.v. formulation was prepared in form of self-nanoemulsifying drug delivery system. Rats were subjected to real-time recording of arterial and ventricular hemodynamics in addition to surface ECG while slow injection of cumulative doses of hinokitiol or plain formulation as well as time control. Key Results: Hinokitiol formulation showed a marked reduction in the elevated systolic pressure (30 mmHg) within only 30 minutes. The decrease in BP seems to be mediated through a reduction in peripheral resistance as appears from the decreases in diastolic pressure, pulse pressure, dicrotic notch pressure, and systolic–dicrotic notch pressure difference. In addition, hinokitiol injection reduced heart load as appears from the decreases in HR and increases in cycle duration (particularly the non-ejection duration), diastolic duration, and decreases in end-diastolic pressure. An effect most likely mediated via prolongation of ventricular repolarization as appears from the increases in QT, QTc, and JT intervals. However, acute i.v. injection of hinokitiol neither affected the baroreflex sensitivity nor sodium/potassium balance. Conclusion and Implications: Acute hinokitiol i.v. markedly reduced severe hypertension. This effect seems to be mediated through decreasing peripheral resistance and decreasing cardiac load suggesting it as an effective treatment in the treatment of hypertensive emergencies, after clinical evaluation.