Nitric oxide and parasympathetic vascular and secretory control of the dog nasal mucosa.

Nasal vascular and secretory responses to local intra-arterial injection of acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) and to electrical stimulation of the nasal parasympathetic nerve fibres were recorded in dogs anaesthetized with pentobarbital. The influence of pretreatment with atropine and propranolol and the nitric oxide synthetase (NOS) inhibitor Nomega-nitro-L-arginine (L-NNA) was analysed. As a marker for NOS, NADPH-diaphorase (NADPH-d) histochemistry was studied in the sphenopalatine ganglion, trigeminal nerve and nasal mucosa. Local intra-arterial infusion of ACh and VIP evoked dose-dependent vasodilatation and nasal secretion which were not modified in the presence of L-NNA. The NO donor nitroprusside induced dose-dependent vasodilatation but no secretion. Atropine did not reduce the vasodilatation evoked by the parasympathetic nerve stimulation, but did reduce the secretory response by 55% (p < 0.05). During L-NNA infusion, the atropine-resistant vasodilatation evoked by parasympathetic nerve stimulation was reduced by a further 80% (p < 0.01) and the non-cholinergic secretory response was reduced by a further 30% (p < 0.05). Simultaneous infusion of the NO donor nitroprusside reversed the secretory response but not the vasodilator response to parasympathetic nerve stimulation. Histochemical studies revealed that NADPH-d activity was co-localized with VIP in parasympathetic axons. These observations suggest that NO could act as a non-cholinergic parasympathetic neurotransmitter in the vascular and secretory control of the dog nasal mucosa.

Effects of calcium channel blockers on cold-induced vasodilatation and elevated sympathetic tone in the canine internal maxillary artery bed.

This study was concerned with the interactive effects of cold-induced vasodilatation, blockade of voltage-sensitive Ca2+ channels and sympathetic nerve stimulation in the nasal vascular bed of anesthetized dogs. To estimate the distribution of the internal maxillary artery blood flow to capillaries and to arteriovenous anastomoses (AVA), the microsphere technique in combination with electromagnetic flowmetry was used. Intraarterial infusion of verapamil resulted in a dose-dependent vasodilatation and a redistribution of the internal maxillary artery blood flow. Simultaneously applied electrical stimulation of the cervical sympathetic trunk resulted in a significant fall in blood flow, caused mainly by a decrease in capillary flow. Verapamil infusion combined with cold exposure led to a simultaneous elevation of the AVA and capillary flows. When electrical stimulation of the cervical sympathetic trunk was also applied, the AVA and capillary flows were affected in different manners, depending on the sequence of the stimulations. Analysis of capillary flow data in the various nasal and facial tissue compartments indicates that cold exposure, blockade of the voltage-dependent Ca2+ channels and an elevated sympathetic tone modify the local nutritive blood flow.

Modulation by neuropeptide Y of parasympathetic nerve-evoked nasal vasodilatation via Y2 prejunctional receptor.

1. In pentobarbitone anaesthetized dogs, preganglionic stimulation of the superior cervical sympathetic nerve (15V, 1 ms, 10 Hz) induced marked reduction of nasal arterial blood flow, whereas parasympathetic nerve stimulation (5 V, 1 ms, 10-30 Hz) evoked frequency-dependent vasodilatation. 2. Sympathetic nerve stimulation for 3 min at 10 Hz evoked significant (P < 0.05) and prolonged attenuation of the vasodilator response to subsequent parasympathetic stimulation. Pretreatment with phentolamine (0.5 mg kg-1 h-1), propranolol (1 mg kg-1) and atropine (0.5 mg kg-1) reduced the vasoconstrictor effect of sympathetic stimulation by 35 +/- 4% whereas the parasympathetic nerve-evoked vasodilatation was not significantly modified. Atropine-resistant parasympathetic vasodilatation remained significantly attenuated for more than 30 min after non-adrenergic sympathetic nerve-evoked vasoconstriction. 3. Vasodilator effects of exogenous vasoactive intestinal polypeptide and peptide histidine isoleucine and vasoconstrictor effects of exogenous neuropeptide Y (NPY) and the NPY analogue [Leu31, Pro34] NPY (Y1-receptor agonist, 8 nmol kg-1), were not altered by adrenoceptor antagonists and atropine f1p4eas the effects of exogenous noradrenaline and acetylcholine were virtually abolished. Attenuation of parasympathetic-evoked vasodilatation could be mimicked by exogenous NPY (8 nmol kg-1) and the NPY analogue, N-acetyl [Leu28, Leu31] NPY 24-36 (Y2-receptor agonist, 20 nmol kg-1) but not by exogenous Y1-receptor agonist. The Y2-receptor agonist did not show significant vasoconstrictor action. 4. It is concluded that sympathetic nerve stimulation attenuates parasympathetic vasodilatation via NPY release acting on prejunctional Y2 receptors.

Circulatory effects caused by intra-arterial infusion of AMP, ADP and ATP in the canine facial and nasal vascular beds.

The effects of the intra-arterial infusion of ATP, ADP and AMP into the internal maxillary artery (IMA), which provides the blood supply to the nasal and forehead regions of the dog, were analyzed. Total blood flow and perfusion pressure measurements in the IMA after administration of each adenyl compound indicated dose-dependent and active vasodilatory responses that were restricted to the ipsilateral vessels. The rank order of potency was ADP > or = ATP > AMP. In order to determine the microcirculatory effects caused by ADP, the tracer microsphere technique combined with absolute blood flow measurement was used. Intra-arterial infusion of ADP in the range 1-200 nmol/min produced elevations in the IMA flow on the stimulated side that ranged between 11 and 74%. The responses to low doses of ADP were mainly confined to the capillaries (CAP), whereas the arteriovenous anastomoses too were sensitive to high doses. The relative contributions of the anatomically and functionally different compartments of the forehead and nose to ADP-produced relaxations of the CAP were dependent upon their location. The CAP flows in the tissues which play a crucial role in conditioning the inspired air increased significantly, while the compartments of the furred surfaces were less sensitive to ADP. The results suggest that, since ATP, ADP and AMP are effective vasodilatory agents in all the regions examined, purines could have a regulatory or modulatory role in the complex vascular regulation of the nasal and forehead regions.

[Mechanism of the vasodilator action of kavinton on the cerebral vessels]. / Mekhanizm vazodilatatornogo deistviia kavintona na mozgovye sosudy.

Experiments on human middle cerebral and cat internal maxillary arteries have shown high vasodilative activity of cavinton. The mechanism of the vasodilative action of the drug involves inhibition of the ingress of exocellular calcium via electrogenic and chemosensitive channels, suppression of calcium mobilization from the intracellular depot with depolarization of the membranes of vascular smooth cells and a decrease in phosphodiesterase activity.

Analysis of cerebrovascular action of diazoxide in conscious goats.

The effects of diazoxide on cerebral blood flow were evaluated in unanesthetized goats under control conditions and after selective blockade of adrenergic or cholinergic receptors in cerebral vessels. Injections of diazoxide (1-27 mg) into the internal maxillary artery produced dose-dependent increases in cerebral blood flow, an increase of 90% occurring with the highest dose. Administration of phentolamine, propranolol, or atropine into the internal maxillary artery did not modify the cerebrovascular response to diazoxide. In reserpine-treated animals the cerebral effects of diazoxide were also unchanged. Intravenous injections of diazoxide (150-400 mg) produced sustained hypotension and tachycardia whereas cerebral blood flow was maintained within normal values or increased slightly. The normal cerebral vasoconstriction obtained with injections of norepinephrine directly into the internal maxillary artery was unaffected during the diazoxide induced-hypotension. These findings show that diazoxide exerts a powerful vasodilatory effect on cerebral vessels through mechanisms other than blockade of alpha-adrenergic receptors or inhibition of adrenergic activity. The results also indicate that activation of beta-adrenergic or atropine-sensitive vascular receptors in the cerebral response to diazoxide is negligible.