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