Pharmacological features of vascular responses of isolated dog and monkey lingual arteries to vasoactive substances.

Using a perfusion technique of isolated vessels, vasoconstrictor responses to alpha-adrenoceptor agonists (norepinephrine [NE], phenylephrine [PE], clonidine, xylazine and tyramine) and KCl were investigated in isolated, perfused dog and monkey lingual arteries. A stainless steel cannula was inserted into the lingual artery segment and perfused with Krebs-Henseleit solution at a constant flow rate. In dog lingual arteries, the agonists induced vasoconstrictions with the following order of potency: NE greater than PE greater than tyramine much greater than clonidine greater than xylazine greater than KCl. In monkey preparations, the order was NE greater than PE much greater than clonidine greater than or equal to tyramine greater than xylazine greater than KCl. In both preparations, NE- and PE-induced constrictions were blocked by bunazosin (an alpha-1 adrenoceptor antagonist), but not influenced by midaglizole (a potent alpha-2 antagonist). Diltiazem (a Ca entry blocker) significantly attenuated NE-induced vasoconstrictions in dog lingual arteries, but did not significantly influence these in monkey preparations. These results suggest that: [1] these arteries contain mostly alpha-1 but scarcely any alpha-2 adrenoceptors; [2] in dog preparations, tyramine induced a marked vasoconstriction which may contribute to investigation on the mechanisms of catecholamine releases from sympathetic nerve terminals; and [3] different blocking effects of diltiazem may indicate that extracellular Ca++ influx may have varying degrees of importance in alpha-1 adrenoreceptor-mediated constrictions in different species, although participation of an intracellular mechanism might not be ruled out.     

Effect of temperature on responses of dog isolated lingual and mesenteric arteries to vasoactive substances

1. The effects of temperature on submaximal vasoconstriction to an intraluminal administration of noradrenaline (NA), phenylephrine, tyramine and KCl were investigated in canine isolated and perfused lingual and mesenteric arteries, using the cannula-inserting method. 2. In lingual arteries, cooling (from 37 to 27 degrees C) caused significant depression of vasoconstriction to the four vasoactive substances used. Rewarming (to 37 degrees C) induced a significant augmentation of constriction by NA, phenylephrine and KCl, but not tyramine. 3. In mesenteric arteries, cooling depressed tyramine- and KCl-induced constrictions, but had no effect on NA- and phenylephrine-induced vasoconstriction. Only in the case of KCl-induced constrictions did rewarming induce a potentiation of the vasoconstrictor response. 4. We conclude that: (i) cooling induces a depression of voltage-dependent Ca2+ channels and rewarming may induce a potentiation of Ca2+ channels in both arteries; (ii) alpha1-adrenoceptor-operated Ca2+ channels are depressed by cooling in lingual arteries but not in mesenteric arteries; and (iii) cooling may induce an attenuation of the re-uptake function in sympathetic nerve terminals in both arteries and this attenuation may be not rapidly restored by acute rewarming.     

Bradykinin-induced coronary chemoreflex in the dog

Summary The injection of 1.0 g of bradykinin into the left coronary artery of anaesthetized dogs produces a simultaneous decrease in blood pressure and heart rate and also a less pronounced decrease in respiratory rate and amplitude. These effects are quite similar, although less intense, to those evoked by equivalent doses of veratrine. Moreover, there is no tachyphylaxis if the interval between injections is kept around 10 min. The cardiovascular changes are proportional to the dose of bradykinin up to 4.0 g; with increasing doses only the hypotensive action is increased. Smaller doses of bradykinin are only effective in the presence of the bradykinin-potentiating-factor, BPF₁₀ (1.0 mg/kg). The bradycardia, but not the hypotension, is potentiated by neostigmine (0.5 mg), and abolished by atropine (1.0 mg/kg). Cervical bilateral vagotomy abolishes the bradycardia and reduces the hypotension elicited by intracoronary bradykinin. When injected into the right atrium bradykinin causes hypotension and an increase in heart rate, even in the presence of BPF₁₀. It is concluded that bradykinin induces a coronary chemoreflex when injected into the coronary artery of the dog.Department of Surgery, Orthopaedics and Traumatology (of the same school).     

Neurogenic responses of urethra isolated from the dog.

Electrical transmural stimulation evoked contraction and relaxation in isolated urethral circular muscle of the dog. The responses were abolished by tetrodotoxin, indicating their neurogenic origin. The contractile force in the middle urethra was greater than that in the proximal and distal urethra. The contractions were not affected by atropine and propranolol, but were completely inhibited by phenoxybenzamine, prazosin and guanethidine. In preparations contracted with prostaglandin F2 alpha, electrical stimulation induced frequency-dependent relaxation in all urethral portions. Atropine, phenoxybenzamine, prazosin and guanethidine had no effect on the relaxation, while propranolol slightly attenuated the relaxation induced at the highest frequency used (5 Hz). The non-adrenergic, non-cholinergic relaxation was also not affected by ketanserin, methysergide, diphenhydramine, alpha,beta-methylene ATP or capsaicin. Exogenously applied phenylephrine and clonidine both produced contractions but the maximal response to clonidine was much smaller than that to phenylephrine. Acetylcholine produced no or feeble contractions. In the preparations contracted with prostaglandin F2 alpha, isoproterenol and vasoactive intestinal polypeptide (VIP) produced relaxation. These results suggest that the circular muscle of dog urethra is reciprocally innervated by sympathetic adrenergic and non-adrenergic, non-cholinergic nerves, and that the neurogenic responses are markedly affected by muscle tension and the portion of the urethra examined.     

Electrophysiological analysis of neurogenic vasodilatation in the isolated lingual artery of the rabbit.

The nature of neurogenic vasodilatation was investigated in isolated segments of rabbit lingual artery. In separate experiments membrane responses to nerve stimulation were studied by use of microelectrodes. In the presence of guanethidine to block constrictor responses and noradrenaline to induce tone, field stimulation with trains of pulses (8 Hz for 0.5 to 4 s) produced vasodilatation. Atropine (10(-6) M) reduced the relaxations to about 50% of the control values while the induced vasodilatations were potentiated by physostigmine. Tetrodotoxin (TTX, 10(-7) M) blocked all nerve-evoked responses. These data suggest that there is a cholinergic and a non-cholinergic component of the vasodilatation produced by nerve stimulation in the rabbit lingual artery. Single stimuli did not evoke electrophysiological responses. With parameters similar to those used in the mechanical studies, periarterial stimulation in the presence of guanethidine evoked membrane hyperpolarizations which achieved amplitudes of up to 11 mV. The ionophoretic application of acetylcholine (ACh) produced hyperpolarization. The inhibitory junction potentials (i.j.ps) but not the ionophoretic-induced responses were blocked by TTX. The nerve-evoked and the ACh-induced hyperpolarizations were potentiated by physostigmine (5 X 10(-7) M) and totally blocked by atropine (10(-7) M). I.j.ps and hyperpolarization to ionophoresis of ACh were recorded from arteries in which the endothelium had been removed by mechanical rubbing. Mechanical relaxation to field stimulation and ACh was observed in preparations without endothelium. These data suggest that the cholinergic component of the neurogenic vasodilatation in the rabbit lingual artery is accompanied by hyperpolarization. The non-cholinergic component does not appear to possess an electrophysiological correlate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypochlorous acid-induced responses in sheep isolated pulmonary artery rings.

The formation of reactive oxygen species (ROS) appears to play a significant role in many pathological states including cystic fibrosis and asthma. Although stimulated inflammatory cells represent a major source of oxygen metabolites and these cells are able to generate the potent oxidant hypochlorous acid (HOCl) effects of HOCl on arteries are not known. HOCl at low concentrations (10(-7)to 10(-4)m) did not affect the resting force or have an action in precontracted sheep pulmonary arteries. HOCl at 10(-4) m concentration reduced histamine-induced relaxations in endothelium intact preparations. However, at high concentrations (10(-2) to 1 m) HOCl led to constriction under resting conditions and caused vasodilation in endothelium intact and denuded serotonin (10 microm) precontracted arteries. These effects of HOCl were significantly reduced by pretreatment of l -arginine (10(-3)m), sodium nitroprusside (SNP, 10(-5) m) and N -acetyl-l-cysteine (NAC, 10(-4) m). The effects of SNP and NAC on HOCl-induced responses were due to direct interaction since only these compounds markedly diminished the HOCl-induced luminol chemiluminescence (CL). Lack of contraction with KCl after high concentrations of HOCl showed that HOCl causes irreversible tissue damage. These results suggest that HOCl produce vasoconstriction under resting force and cause vasodilation when the pulmonary arteries precontracted. HOCl may interact with endothelium-derived mediators and contribute to tissue injury and vascular dysfunction seen in disease states.     

Coronary vascular responses to nicotine in the anaesthetized dog

Summary The effect of the intra-coronary (i.c.) injection of nicotine on large coronary artery diameter and coronary blood flow was examined in anaesthetized dogs. In sixteen untreated dogs nicotine (20 g i.c.) had a biphasic effect on arterial pressure (initial increase, 7 ± 2 mmHg; secondary decrease, –8 ± 3 mmHg) which was accompanied by small and variable effects on heart rate and an increase in LV dP/dt. Nicotine increased large coronary artery diameter by 5.8 ± 0.8% but had a biphasic effect on coronary blood flow (initial increase, 41 ± 7 ml/min; secondary decrease, –10 ± 2 ml/min). Bilateral vagotomy or muscarinic receptor blockade with atropine (0.1 mg/kg i. v.) did not significantly affect the nicotine-induced changes in coronary artery diameter or coronary blood flow. The additional antagonism of -adrenoceptors with propranolol (1 mg/kg i. v.) abolished the effect of nicotine in coronary artery diameter ( CD = 0.2 ± 0.2%) and the initial increase in coronary blood flow ( CBF = 1 ± 1 ml/min) but enhanced the secondary decrease in flow ( CBF = –25 ± 3 ml/min). The nicotine-induced decrease in coronary blood flow observed after muscarinic and -adrenoceptor blockade was attenuated by antagonism of ₁-adrenoceptors with prazosin (10 g/kg i. c., CBF = –15 ± 3 ml/min) and abolished after additional antagonism of ₂-adrenoceptors with idazoxan (50 g/kg i. c., CBF = –2 ± 1 ml/min). These results indicate that in the anaesthetized dog intra-coronary injection of nicotine results in -adrenoceptor mediated dilatation of both large and small coronary arteries. In the coronary resistance vessels, but not in the large coronary artery, the dilatation is opposed by ₁-and ₂-adrenoceptor mediated vasoconstriction. Send offprint requests to O. L. Woodman at the above address     

Bradykinin-induced endothelium-dependent relaxation of bovine intrapulmonary artery and vein

Bradykinin induced relaxation and cyclic GMP accumulation in both bovine intrapulmonary artery and vein. Both the relaxant responses and the accompanying cyclic GMP accumulations were abolished or markedly reduced by intimal rubbing or pretreatment with the guanylate cyclase inhibitor, methylene blue. These findings indicate that both bovine intrapulmonary artery and vein exhibit endothelium-dependent relaxation in response to bradykinin, and that the relaxant responses in both vessels are associated with cyclic GMP accumulation.     

Positive chronotropic and inotropic responses to guanosine in the isolated dog atrium.

The effects of guanosine on chronotropism and inotropism in isolated dog atria were studied in spontaneously beating preparations which were suspended in a bath perfused with arterial blood from a carotid artery of a heparinized support dog. Guanosine administered into the cannulated sinus node artery in a dose range of 30 microgram to 3 mg produced a dose-related positive inotropic and chronotropic effect. The positive responses to guanosine were not inhibited by treatment with propranolol or a non-depressant beta-blocker, carteolol, in doses which blocked responses to norepinephrine. From these results, it is concluded that guanosine has a direct effect on atrial rate and contractility.     

Epinephrine facilitates neurogenic responses in isolated segments of dog mesenteric arteries

Epinephrine (EPI) bitartrate (10(-9)-10(-8) M) significantly enhanced tension development in response to electrical field stimulation in isolated segments of dog mesenteric arteries. Responses to exogenous norepinephrine (NE) were generally unaffected, indicating that the EPI-induced increases in response to field stimulation are not explicable in terms of changes in postjunctional sensitivity. The facilitatory effects of EPI (5 X 10(-9) M) were unaffected by atenolol (10(-6) M) but were completely abolished by timolol (2 X 10(-7) M), suggesting an involvement of beta 2-adrenoreceptors in mediating the EPI-induced facilitation of neurogenic responses. Responses to exogenous NE were usually unaffected by either beta-adrenoreceptor antagonist. The results suggest that release of endogenous sympathetic neurotransmitter, measured in terms of postjunctional effects on vascular smooth muscle tone, appears to be modulated by prejunctional facilitatory beta 2-adrenoreceptors and that these receptors may be a physiologic site of action of EPI.     

Bradykinin-induced airway responses in guinea pig: effects of inhibition of cyclooxygenase and thromboxane synthetase.

We studied the effects of indomethacin (10 mg/kg i.v.), a cyclooxygenase inhibitor, and OKY-046 (1, 10 and 30 mg/kg i.v.), a selective thromboxane synthetase inhibitor, on airflow obstruction and airway plasma exudation induced by bradykinin (150 nmol) instilled by the airway route to anesthetized guinea pigs. To do this, we studied changes in lung resistance (RL) and extravasation of Evans Blue dye respectively. Instilled bradykinin produced an immediate and marked increase in RL which peaked at approximately 30 s. We also observed a delayed increase in RL, reaching a second peak at approximately 3 min. Bradykinin produced airway plasma exudation at all airway levels, measured as extravasation of Evans Blue dye. Indomethacin significantly inhibited both the immediate and the delayed increase in RL after bradykinin. OKY-046 had a similar significant and dose-dependent inhibitory effect on these responses. In addition, both drugs inhibited bradykinin-induced Evans blue dye extravasation in intrapulmonary airways. Bradykinin instilled by the airway route significantly decreased systemic blood pressure but this effect was not altered in animals pretreated with either indomethacin or OKY-046. We conclude that the bronchoconstrictor response and airway plasma exudation induced by instilled-bradykinin may be mediated in part via thromboxane A2 generation.     

UTP induces vascular responses in the isolated and perfused canine epicardial coronary artery via UTP-preferring P2Y receptors

1. Vasoconstrictor responses of the isolated and perfused canine epicardial coronary artery to uridine 5′-triphosphate (UTP) were analysed pharmacologically.
2. At basal perfusion pressure, UTP induced vasoconstriction in a dose-related manner and the vasoconstriction was sometimes followed by a slight vasodilatation at large doses (more than 10 nmol). The rank order of potency for vasoconstriction was UTP=UDP>ATP>TTP⩾ITP>> UMP. At raised perfusion pressure by 20 mM KCl, the vasoconstriction was not changed and a small vasodilatation was induced at large doses. The rank order of potency for vasodilatation was induced at large doses. The rank order of potency for vasodilatation was ATP>>ITP⩾UDP>UTP⩾TTP. The maximal vasodilator response to UTP was much less than that to ATP. UMP did not induce vasodilatation.
3. The P2X receptor agonist and desensitizing agent α,β-methylene ATP (1 μM) and the P2 receptor antagonist suramin (100 μM) inhibited the vasoconstrictor responses to ATP but not those to UTP and UDP. The P2 receptor antagonist reactive blue 2 (30 μM) did not inhibit the vascular responses to UTP.
4. UTP (200 μM) desensitized the vasoconstrictor responses to UTP, but not either the vasodilator responses to UTP or the vasoconstrictor responses to ATP and UDP. UDP (200 μM) did not desensitize the vascular responses to UTP.
5. Preincubating the UDP stock solution and arterial preparation with hexokinase (10 and 1 uml⁻¹, respectively) did not change the vasoconstrictor responses to UDP.
6. The Ca channel blocker diltiazem (1 μM) inhibited the vasoconstrictor responses to UTP but not those to ATP and UDP. Incubation in a Ca²⁺-free solution containing 1 mM EGTA inhibited the vascular responses to ATP, UTP and UDP.
7. Removal of the endothelium by an intraluminal injection of saponin (1 mg) inhibited the vasodilator responses to UTP. Indomethacin, a cyclo-oxygenase inhibitor (1 μM), inhibited the vasodilator responses to UTP, but N^G-nitro-L-arginine, a nitric oxide synthase inhibitor (300 μM), did not have an inhibitory effect.
8. The results suggest that (1) UTP induces vasoconstriction via UTP-preferring P2Y receptors on the smooth muscle and vasodilatation via receptors different from those mediating the vasoconstriction induced by UTP and mediating the vasodilatation by ATP on the endothelium, through mainly the release of prostacyclin in the canine epicardial coronary artery; (2) UDP induces vasoconstriction via UDP-preferring P2Y receptors; and (3) L-type Ca ion channels are involved in the vasoconstriction induced by UTP, but not in that induced by UDP.

     

Triphasic vascular responses to bradykinin in the mesenteric resistance artery of the rat.

The vascular effects of bradykinin were studied in rat perfused mesenteric vascular beds with active tone. Bolus injections of bradykinin (1-1000 pmol) but not des-Arg(9)-bradykinin (bradykinin B(1) receptor agonist) induced triphasic vascular responses: the initial sharp vasodilation followed by transient vasoconstriction and subsequent gradual vasodilation. The triphasic vascular responses to bradykinin were abolished by FR 172357 (3-bromo-8-[2,6-dichloro-3-[N-[(E)-4-(N,N-dimethylcarbamoyl) cinnamidoacetyl]-N-methylamino]benzyloxy]-2-metylimidazo[1,2-a]pyridine) (bradykinin B(2) receptor antagonist, 0.1 microM). Endothelium removal with sodium deoxycholate and N(w)-nitro-L-arginine (300 microM) abolished the bradykinin-induced initial sharp vasodilation. Indomethacin (0.5 microM) and seratrodast (thromboxane A(2) receptor antagonist, 0.5 and 5 microM) abolished the bradykinin-induced second vasoconstriction. The bradykinin-induced third vasodilation was abolished by capsaicin (1 microM) and calcitonin gene-related peptide (CGRP)-(8-37) (CGRP receptor antagonist, 0.5 microM). These findings suggest that the bradykinin-induced initial sharp vasodilation is endothelium dependent, that endogenous thromboxane A(2) is involved in the second vasoconstriction, and that the third slow vasodilation is produced by activation of capsaicin-sensitive CGRP-containing nerves.     

Effects of cinepazide on the purinergic responses in the dog cerebral artery

The effects of cinepazide, 1-[(1-pyrrolidinylcarbonyl)methyl]-4-(3,4,5-trimethoxycinnamoyl )piperazine hydrogen maleate, were studied in isolated dog cerebral arteries. Cinepazide in concentrations ranging from 10(-6) to 10(-5) M augmented the relaxing responses to ATP, adenosine and cAMP. However, this agent did not affect the relaxations induced by isoproterenol and papaverine and the contractions induced by 5-HT, prostaglandin F2 alpha and ATP. In the basilar artery preloaded with 3H-norepinephrine or 3H-adenosine, electrical transmural stimulation resulted in a marked increase in 3H-efflux. This efflux accompanied an initial transient contraction followed by a relaxation. Cinepazide slightly reduced the 3H-efflux evoked by electrical stimulation. However, the relaxing response was mostly augmented by the treatment with cinepazide. The relaxing responses to ATP, adenosine, cAMP and electrical transmural stimulation were attenuated by theophylline. These results suggest that cinepazide selectively potentiates the relaxing response mediated through purinergic P1-receptors.     

A method for recording smooth muscle and vascular responses of the blood-perfused dog trachea in situ.

1 A method is described for measuring responses of dog tracheal musculature and vasculature in situ. 2 The upper two thirds of the trachea was perfused with blood through both cranial thyroid arteries at a constant pressure. The blood flow through the arteries was measured with an electromagnetic flowmeter. The response of the tracheal musculature was measured as a change in pressure in a water-filled cuff inserted into the trachea via the mouth. Drugs were injected close-arterially. 3 Acetylcholine produced dose-dependent increases in blood flow rate (vasodilatation) and in tracheal intraluminal pressure (tracheal constriction). These responses were antagonized by atropine. 4 Isoprenaline produced vasodilatation which was blocked by propranolol. Adrenaline and noradrenaline caused vasocontriction which was blocked by phentolamine. 5 All three catecholamines produced a decrease in tracheal intraluminal pressure (tracheal dilatation). The tracheal dilatation in response to adrenaline and noradrenaline was converted to constriction by propranolol. The tracheal constriction thus unmasked was abolished specifically by phentolamine. 6 From these results it is concluded that the tracheal musculature and vasculature contain muscarinic receptors, and excitatory alpha- and inhibitory beta-adrenoceptors. In the tracheal musculature beta-adrenoceptors predominate over alpha-adrenoceptors; the reverse is true in the tracheal vasculature.     

Chemical removal of the endothelium by saponin in the isolated dog femoral artery

Chemical removal of the endothelium by saponin in the isolated dog femoral artery was investigated by comparing the relaxant responses to endothelium-dependent and -independent vasodilators of saponin-treated rings with the responses of non-treated rings. Saponin treatment was done by incubating rings with Krebs-Henseleit solution containing 0.1, 0.3 or 1 mg/ml of saponin for 45 min at 37 degrees C. In non-treated rings, acetylcholine (10(-8)-3 X 10(-6) M) caused a concentration-dependent relaxation of rings precontracted with prostaglandin F2 alpha (3 X 10(-6) M). The acetylcholine-induced relaxation was reduced in rings pretreated with 0.1 mg/ml of saponin and almost abolished with 0.3 or 1 mg/ml. Prostaglandin F2 alpha-induced contraction was suppressed weakly by treatment with 0.3 mg/ml and markedly with 1 mg/ml saponin. The treatment with 0.3 mg/ml saponin markedly reduced relaxations caused by substance P (10(-9)-3 X 10(-8) M) and by Ca2+-ionophore A23187 (10(-6) M). Relaxant responses of saponin-treated rings to nitroglycerin and to nitroprusside were almost identical with those of non-treated rings. These results showing selective suppression by saponin of the endothelium-dependent relaxation suggest that saponin removes the endothelial cells from the intimal surface of the artery, and this was confirmed by electron microscopy. The endothelium removing method with saponin seems to be useful as a pharmacological tool for vascular investigations.     

Double-peaked positive chronotropic responses of isolated and cross-perfused dog atria to ATP

The effects of a large amount of adenosine and ATP (100 to 3000 micrograms) were investigated on sinus rate and developed tension, using the isolated dog atrium which was perfused with arterial blood from a heparinized donor dog. Each of the substances used for study was administered into the cannulated sinus node artery of the isolated atrium. Adenosine caused monophasic negative chronotropic and inotropic effects in a dose-related manner. However, ATP induced two-peaked positive chronotropic phases during a long-lasting negative chronotropic phase, i.e., initially, brief positive (t-1) effects and secondarily, relatively longer positive chronotropic (t-2) effects. These responses were repetitively induced during the experiment. The t-1 and t-2 were not influenced by treatment with propranolol which significantly blocked the positive chronotropic effect of norepinephrine. Aminophylline treatment significantly suppressed t-2 but not t-1. Quinidine (100-1000 micrograms) did not affect either the t-1 or t-2. It is suggested that ATP-induced tachycardia in the dog is partially due to activation of the P1-purinoceptors named by Burnstock.     

Adenylate cyclase-mediated vascular responses of rabbit aorta, mesenteric artery and skin microcirculation.

1. The importance of adenylate cyclase-mediated vascular relaxation in the macro and microcirculation was assessed in rabbit aortic and coeliac artery bioassay rings in vitro and skin microvessels in vivo. 2. The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38), the beta-agonist, isoprenaline, and the prostaglandins, PGE1 and PGE2, were compared with the activity of nitroprusside, which acts by stimulating guanylate cyclase. 3. In aortic tissue the relative relaxant potencies were (-log M EC50, 100% = response to nitroprusside 10(-6) M): nitroprusside 7.0, PACAP38 6.8, isoprenaline 6.3; PGE1 and PGE2 were weak constrictors. In coeliac artery rings relative potencies were (-log M EC50, 100% = response to nitroprusside 10(-5) M): PACAP38 6.6, PGE1 6.6, nitroprusside 6.5, PGE2 4.9, and isoprenaline 4.3. 4. Comparative potencies when injected into anaesthetized rabbit skin in vivo were (-log mol/site required to increase blood red cell flux by 75%): PACAP38 13.0, PGE2 10.7, isoprenaline 9.7, PGE1 9.1, nitroprusside < 7. 5. Nitroprusside, the most effective relaxant tested in the aorta, was 10(7) fold less potent than PACAP in its effect on skin blood flow. PGE1 and PGE2 were constrictors of the aorta, of intermediate effect in the coeliac artery, but potent vasodilators of the microcirculation. 6. In this model, the importance of adenylate cyclase-mediated vascular relaxation increases with decreasing vessel size.     

Vasomotor responses in the isolated perfused external and internal carotid vascular beds of the rat.

1. The external (ECB) or the internal (ICB) carotid vascular beds of the rat were isolated and perfused with Krebs-Henseleit solution at constant flow (1 ml/min). Changes in perfusion pressure (PP) were recorded after cervical sympathetic stimulation and after the administration of norepinephrine (NE) and serotonin (5-HT). 2. Sympathetic stimulation induced an increase in PP (vasoconstriction) in both vascular beds, however, this effect was significantly higher in the ECB than in the ICB. 3. Exogenous NE also induced a significantly higher contractile response in the ECB. 4. Prazosin (10(-8) M) significantly inhibited the response to sympathetic stimulation and to NE both in the ECB and in the ICB, but yohimbine (10(-7) M) had no effect, suggesting that the vasoconstriction was mainly due to the activation of alpha 1-adrenoceptors. 5. 5-HT induced a contractile response both in the ECB and the ICB. In contrast with the response to NE, the contraction induced by 5-HT in the ICB was significantly higher than in the ECB. 6. Ketanserine (10(-8) M) antagonised both responses, indicating the involvement of 5-HT2 receptors. 7. The contractile effect of 5-HT in the ECB was significantly enhanced by a subthreshold sympathetic stimulation that did not modify the PP by itself. This effect was not seen in the ICB. 8. The differential perfusions of the ECB or the ICB demonstrated a different reactivity of ECB and ICB, both to sympathetic stimulation and to the administration of exogenous NE or 5-HT. 9. Furthermore, the response to 5-HT in the ECB was modulated by a subthreshold sympathetic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)