Judit Kapocsi

Chemical neuroprotection in the cochlea: The modulation of dopamine release from lateral olivocochlear efferents

The prevalence of sensorineural hearing loss is increasing worldwide, mainly due to ageing, increased noise exposure and cardiovascular risk factors. Several papers dealt with the mechanisms underlying the primary causes of impaired hearing and eventual deafness, including the damage and loss of auditory hair cells; however, very little is known about the protective mechanisms that exist for hearing. Several recent investigations have implicated dopamine (DA) in a neuroprotective circuit for the cochlea. The lateral olivocochlear (LOC) efferents provide axonal innervation of the inner hair cell afferent synapses and release DA and other substances in response to different stimuli. Under ischemic conditions or during noise exposure, DA has been proven to play a neuroprotective role against glutamate excitotoxicity. This review summarises what is currently known about the modulation of DA release in the cochlea, using primarily in vitro experimental data. Based on recent knowledge, there could be two functional subgroups within the LOC fibres, i.e., the DA- and GABA-containing projections. In this review, we attempt to show the neurochemical interactions between these two subsystems. Other aspects of cochlear neurotransmission are also discussed to provide a complete picture of cochlear dopaminergic function in physiological and pathophysiological cases with particular reference to excitotoxicity.

The effect of low-dose carvedilol, nebivolol, and metoprolol on central arterial pressure and its determinants: a randomized clinical trial.

In this prospective, open‐label, randomized, controlled clinical trial the effects of low‐dose carvedilol, nebivolol, and metoprolol on central arterial pressure and augmentation index (AIx) and its heart rate–corrected value (AIx@75) were assessed. The authors randomized 75 hypertensive patients (18–70 years) to carvedilol 12.5/25 mg, metoprolol 50/100 mg, or nebivolol 2.5/5 mg daily and followed them up for 3 months. Central arterial pressure and AIx were measured with applanation tonometry at baseline and at the end of follow‐up. Analyses were restricted to 60 completers. Central systolic pressure decreased equally in all 3 treatment arms. AIx remained unchanged, while AIx@75 decreased significantly by 5.4%±2.5% in the nebivolol group. According to general linear models, individual change in heart rate was a strong predictor of change in AIx in the carvedilol group (r2=0.23, P=.03) although no similar association was found in the nebivolol group (r2=0.09). The impact of β‐blockers with vasodilator effects on pressure augmentation seems to be different with nebivolol having the largest potential of decreasing AIx@75. While AIx changes associated with carvedilol treatment are strongly driven by heart rate changes, those associated with nebivolol treatment seem to be the result of other mechanisms.

Effects of clonidine and guanfacine in essential hypertension

Daily doses of 0.3 mg clonidine and 3 mg guanfacine were equiactive in decreasing blood pressure and heart rate in 17 subjects with essential hypertension. Clonidine decreased cardiac output and guanfacine decreased total peripheral resistance, while clonidine had no effect on stroke volume but guanfacine increased it. Both clonidine and guanfacine decreased plasma renin activity. Naloxone, 0.4 mg iv, reversed the antihypertensive effect of clonidine but was ineffective even at higher doses (1.6 mg iv) when subjects were treated with placebo or guanfacine. It is suggested that the hemodynamic differences between the two centrally acting α2‐adrenoceptor agonist antihypertensive drugs may at least in part result from the involvement of opioid mechanisms only in the action of clonidine.

Effect of prazosin and oxprenolol on plasma renin activity and blood pressure in patients with essential hypertension.

48 patients with normal-renin essential hypertension were treated with prazosin alone or in combination with oxprenolol. 1 h after a single dose of 2 mg prazosin tachycardia and a decrease in blood pressure developed. Renin activity in the peripheral plasma (PRA) increased from 1.04 +/- 0.15 to 2.64 +/- 0.20 ng AgT/ml/h. A 3-day treatment with 2 mg t.i.d. prazosin of 11 patients caused no further decrease in blood pressure, while PRA returned to the baseline level. Treatment for 3 days with 2 mg prazosin t.i.d. and 40 mg oxprenolol t.i.d. of 37 patients further decreased blood pressure as well as PRA. The increase in PRA after a single dose of prazosin could be related to the enhanced sympathetic activity. The decreased PRA after prazosin + oxprenolol therapy may be one of the factors responsible for the greater antihypertensive response to the combined therapy.