Early investigations have suggested a relationship between hypertension and melatonin, a pineal hormone. The aims of this study were to evaluate the implication of the sympathetic nervous system in the acute effect of melatonin on blood pressure in conscious 12-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), and to determine whether the hypotensive effect of melatonin is associated with alterations in pre- or postsynaptic mechanisms. Melatonin, 10 mg/kg, produced a sustained time-dependent decrease of mean arterial pressure only in SHR without changes in heart rate in both groups. Until 20 min after melatonin administration, plasma epinephrine (EPI) levels were reduced by about 60% in both groups, but norepinephrine (NE) levels were decreased only in SHR by about 30%. The nitroprusside-induced hypotension responses and the associated increases in heart rate were similar in both groups before or after administration of melatonin. Unexpectedly, the sympathetic reactivity to nitroprusside, evaluated by the increases in NE and EPI, was markedly enhanced after melatonin treatment in both WKY and SHR. The stimulation induced [3H]-norepinephrine release from isolated atria was not altered by melatonin in SHR. In cultured aortic vascular smooth muscle cells, the basal and phenylephrine induced inositol phosphate formations were greater in SHR, and the melatonin pretreatment dose dependently attenuated the phenylephrine responses in cells from both WKY and SHR. Therefore the hypotensive action of melatonin appears to be associated with an inhibition of basal sympathoadrenal tone and could also be mediated partly by the blockade of postsynaptic alpha1-adrenergic receptor-induced inositol phosphate formation.

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Purpose:To assess the effect of preservative-free dorzolamide–timolol on nonvisual symptoms and intraocular pressure (IOP) in newly diagnosed and untreated patients with open-angle glaucoma or ocular hypertension.Methods:This was a prospective, 8-week, open-label, Canadian multicenter study. All patients were treated with preservative-free dorzolamide–timolol formulation. The primary outcome was the change in the nonvisual symptom score of the Glaucoma Symptom Scale (GSS-SYMP-6) from baseline to 8 weeks. Secondary effectiveness outcome measures were absolute and percent changes in IOP from baseline to 4 and 8 weeks.Results:One hundred and seventy-eight patients were enrolled. Mean (SD) age was 65.6 (12.1) years and 90 (50.6%) were females. There were 92 patients diagnosed with open-angle glaucoma, 62 with ocular hypertension, and 23 with both diseases (diagnosis was missing for one patient). The mean (SD) GSS-SYMP-6 score increased from 73.6 (21.8) at baseline to 76.1 (20.7) at 8 weeks (P = 0.097). Mean (SD) IOP significantly decreased by 11.7 (5.1) mmHg at 4 weeks (P < 0.001) and by 11.5 (5.3) mmHg at 8 weeks (P < 0.001), representing reductions of −38.5% (P < 0.001) and −38.0% (P < 0.001), respectively.Conclusion:Preservative-free dorzolamide–timolol does not increase eye discomfort while significantly reducing IOP in patients with open-angle glaucoma or ocular-hypertension.

4 The effect of BK was not affected by diclofenac (1 fiM), a cyclo-oxygenase inhibitor. Bisindolylmaleimide (1 gLM), a protein kinase C inhibitor, significantly reduced the facilitatory effect of BK (10 nM), angiotensin II (0.3 p4M) and phorbol dibutyrate (0.1 and 1 f1M) but not of fenoterol (1 fM). 5 The results suggest that BK enhances noradrenaline release via a prejunctional B2 kinin receptor in the rat atrium. The effect appears to involve protein kinase C as a second messenger.

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