vasoactive-intestinal-peptide and vinpocetine

Increased concentration of manganese (Mn) in the brain is known to be associated with excitotoxicity and neuroinflammation. Vinpocetine, an alkaloid derived from the plant Vinca minor L., basically shows its effect via phosphodiesterase inhibition and voltage-dependent Na

Topics: Cell Death; Cell Line; Dose-Response Relationship, Drug; Humans; Manganese; Membrane Potential, Mitochondrial; Neural Stem Cells; Reactive Oxygen Species; Vasoactive Intestinal Peptide; Vinca Alkaloids

In the coronary circulation, endothelin-1 (ET-1) evokes spasms which are difficult to treat when the endothelial integrity is compromised. This study compares several classes of relaxing agents on already established contractions to ET-1 in an in vitro model using ring segments of the porcine left descending coronary artery (pLAD). All segments were precontracted with 10 nmol/L ET-1. The calcium channel blocker isradipine was 300 times more potent than verapamil, but was only a partial relaxant; the maximal relaxation obtained was 52 +/- 2% (n = 6). Atrial natriuretic peptide (ANP) was an equally potent relaxant of the ET-1 contraction; however, it too was an incomplete relaxant, maximal relaxation being < 60%. A 50% relaxation of the ET-1 contraction was obtained with 0.28 +/- 0.24 mumol/L ANP, n = 4 (IC50). Comparison of cyclic nucleotide analogues revealed a 30 times higher potency for 8-bromo-cyclic guanosine monophosphate (8-Br-cGMP)(IC50 44 +/- 11 mumol/L, n = 6) than for 8-bromo-cyclic adenosine monophosphate (8-Bi-cAMP) (IC50 1600 mumol/L, n = 6). The cyclic nucleotide phosphodiesterase (PDE) inhibitor milrinone, a PDE 3-inhibitor with an IC50 2.4 +/- 1.8 mumol/L, (n = 6) was 10 times more potent than rolipram (PDE 4-inhibitor), zaprinast (PDE 5-inhibitor) and vinpocentine (PDE 1-inhibitor). Withdrawal of these analogues and inhibitors from segments continuously exposed to 10 nmol/l ET-1 revealed that vinpocentine and 8-Br-cGMP were irreversible relaxants, in contrast to milrinone and 8-Br-cAMP. In conclusion, this study has demonstrated that cGMP-enhancing agents, such as the naturally occurring ANP, the calcium channel blocker isradipine, and the synthetic inhibitor of PDE 3, were the most effective relaxants of ET-1 evoked contractions in pLAD in vitro.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Animals; Atrial Natriuretic Factor; Caffeine; Calcium Channel Blockers; Calcium Channels; Calcium Channels, L-Type; Colforsin; Coronary Vessels; Cyclic AMP; Cyclic GMP; Dose-Response Relationship, Drug; Endothelin-1; In Vitro Techniques; Isradipine; Milrinone; Muscle, Smooth, Vascular; Papaverine; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Purinones; Pyrrolidinones; Rolipram; Swine; Vasoactive Intestinal Peptide; Vasoconstriction; Vasodilation; Verapamil; Vinca Alkaloids

Aminophylline or VIP (Vasoactive Intestinal Peptide) given ip. or iv. have marked bronchodilatory effects. The onion extracts protect guinea pigs as well as human patients against allergen-induced bronchial spasms (Dorsch et al.). Recently it has been shown that lipophilic components of onions seem to be responsible for the antiasthmatic effects. The purpose of this study was to investigate the effect of intracerebrally injected aminophylline (3 microM), Vinpocetinum (0.1 mg/kg), VIP (5 micrograms) and onion oils (30 microliters of extracts) on the respiratory center and on the resistance of lower airways of rats. The following respiratory parameters were evaluated: respiratory rate (RR), tidal volume (VT), mean inspiratory flow (Vin), respiratory minute volume (VE), and dynamic lung resistance (R). Respiratory rate was increased and values of all the other parameters were decreased after aminophylline treatment. VIP increased the tidal volume, minute ventilation and the respiratory drive. After injection of onion extracts the respiratory rate and the dynamic lung resistance decreased, but the tidal volume increased. The beneficial effects of onion oil are manifested not only peripherally acting on bronchial smooth muscle but via the reflexogenic pathways.

Topics: Airway Resistance; Allium; Aminophylline; Animals; Lung Volume Measurements; Male; Plant Extracts; Pulmonary Ventilation; Rats; Rats, Inbred Strains; Respiratory Center; Vasoactive Intestinal Peptide; Vasodilator Agents; Vinca Alkaloids