Heterogeneity in the response to dopamine of monkey cerebral and peripheral arteries

In helical strips of monkey cerebral and mesenteric arteries contracted with prostaglandin F2 alpha, dopamine in low concentrations produced a moderate relaxation but in high concentrations produced a contraction from the level of relaxation. On the other hand, coronary, renal, and femoral arterial strips responded to dopamine with only a concentration-dependent contraction. Treatment with phenoxybenzamine or phentolamine potentiated the dopamine-induced relaxation seen in cerebral and mesenteric arteries and reversed the contraction in the other arteries to a relaxation. After treatment with phenoxybenzamine, relaxant responses to dopamine of cerebral, mesenteric, and renal arteries were almost identical, and, compared with those, the responses of coronary and femoral arteries were appreciably less. Relaxations induced by dopamine were not influenced by propranolol, atropine, aminophylline, cimetidine, and aspirin but were markedly attenuated by droperidol. Adenosine-induced relaxations were not affected by droperidol. It is concluded that dopamine preferentially relaxes monkey cerebral and mesenteric arteries, possibly via dopaminergic receptors. It appears that the dopamine-induced contractions mediated by alpha-adrenoceptors predominate over the relaxation in coronary, renal, and femoral arteries, and dopaminergic receptor function is greater in cerebral, mesenteric, and renal arteries than in coronary and femoral arteries.     

Diminished arterial smooth muscle response to adenosine during Na-K pump inhibition

The possibility of a role of the sarcolemmal Na-K pump of arterial smooth muscle in the mechanism of action of adenosine was explored in this study. Isolated helical strips of rabbit coronary and femoral arteries were suspended in organ baths with physiological salt solution, and isometric contractions were recorded. Concentration-dependent relaxations produced by adenosine were attenuated during Na-K pump inhibition. Quabain (1 x 10^–5 M) significantly increased the adenosine ED₅₀ values from 9.6 x 10^–8 M to 2.9 x 10^–7 M and from 9.4 x 10^–7 M to 8.4 x 10^–6 M in coronary and femoral artery strips, respectively. Similar results were obtained by substitusions of LiCl for NaCl in the bathing solution and with a K-free solution. These effects were not attributable to augmented initial active tension, time-dependent changes in adenosine response or the release of norepinephrine from adrenergic nerve terminals. In addition, adenosine enhanced potassium-induced relaxation, and index of Na-K pump activity in isolated vascular strips. The data suggest that sarcolemmal Na-K pump activity may contribute directly or indirectly to the mechanism of action of adenosine.     

Potassium-induced relaxation in isolated cerebral arteries contracted with prostaglandin F2α

Summary In helically cut strips of canine cerebral arteries exposed to 5.4 mM [K⁺]_o and contracted with prostaglandin F₂, the addition of K⁺ in concentrations ranging from 0.5–5 mM caused a dose-related relaxation. The relaxing effect of K⁺ was potentiated at reduced [K⁺]_o and suppressed at reduced [Na⁺]_o. Reduction of Cl^– from bathing media failed to alter the effect of K⁺. Removal of external Ca²⁺ markedly attenuated the K⁺-induced relaxation and increase in [Ca²⁺]_o also attenuated the relaxation. Similar relaxation was induced by K⁺ in cerebral arteries from other species including humans, puppies, cats and rabbits. The addition of K⁺ also elicited a relaxation in peripheral arteries, including coronary, femoral, mesenteric and renal, contracted with prostaglandin, but this relaxation was markedly less than in cerebral arteries. The content of Na⁺ in freshly excised cerebral arteries was significantly greater than that of peripheral arteries, while the content of K⁺ in these arteries was not significantly different.The present study provides further evidence to support the hypothesis that an electrogenic Na⁺ pump is involved in the genesis of K⁺-induced relaxation. The Na⁺ pump does not appear to be fully activated at normal [K⁺]_o of 5.4 mM in cerebral arteries.     

Ultrastructural localisation of serotonin and substance P in vascular endothelial cells of rat femoral and mesenteric arteries

Summary An electron microscopic-immunocytochemical study has been made on the localisation of serotonin and substance P in endothelial cells of femoral and mesenteric arteries of the rat. In the femoral and mesenteric arteries, less than 10% of the endothelial cells showed positive immunolabelling for these substances. The distribution of serotonin and substance P in endothelial cells was similar in both arteries. The immunoprecipitate was confined to the cytoplasm, including subcellular organelles. The results are discussed in terms of endothelial mechanisms of local control of blood flow.     

Arterial size determines the enhancement of contractile responses after suppression of endothelium-derived relaxing factor formation

We studied the effect of endothelium-derived relaxing factor (EDRF) on norepinephrine-induced contractile responses and on the tissue guanosine-3,5-phosphate (cGMP) concentration of isolated rabbit arteries with an increasing endothelium to smooth muscle cell ratio (aorta, femoral and mesenteric arteries). After suppression of EDRF formation (either by N ^G-nitro-l-arginine or, in mesenteric arteries, by saponin), contractions elicited by cumulative doses of norepinephrine were unaltered in aorta but were enhanced by 22.5% in femoral arteries and by 44.3% in mesenteric arteries (at the highest norepinephrine concentration). The cGMP concentration (pmol/mg protein) of unstimulated, endotheliumintact vessels decreased after suppression of EDRF formation from 1.09±0.24 to 0.74±0.28 in aortic, from 2.86±0.4 to 0.61±0.19 in femoral and from 6.3±0.9 to 0.7±0.15 in mesenteric arterial segments. The basal cGMP concentration did not differ in endothelium-denuded segments of these arteries, suggesting a similar basal activity of soluble guanylate cyclase (sGC). A higher sensitivity of sGC may have contributed to the higher cGMP concentration observed in the smaller arteries, since in the presence of sodium nitroprusside the cGMP concentration of endothelium-denuded segments increased 1.8-fold in aortic, 2.9-fold in femoral and 2.4 fold in mesenteric arterial segments. However, these differences in sGC activation cannot be solely responsible for the high basal cGMP concentration in endotheliumintact mesenteric arteries. The greater ratio of endothelium to smooth muscle cell layers in the smaller arteries might result in a higher EDRF concentration in the vascular wall and subsequently in a higher cGMP concentration. In conclusion, these data support the view of a greater importance of EDRF-mediated vascular control in small arteries than in large conduit arteries.     

Length-tension relationships in resting and activated vascular smooth muscle fibres

Summary The length-tension relationships of resting or activated (by 130 mM of potassium) helical strips of the pig coronary artery were studied. The distensibility of the preparations was expressed by approximated exponential function. In non-activated strips, an average lengthening of 9.64% was necessary for doubling the resting tension. The maximum of active tension (isometric contractions) occurred at high degrees of muscle stretch, whereas the maximum of shortening (isotonic free-loaded contractions) was found at lower values of resting tension. If the theory of the sliding mechanism is a correct assumption for the contraction process of vascular smooth muscle, the maximum of active tension observed at a muscle stretch of about 8000 dynes/mm² is obviously caused by an optimal overlapping of actin and myosin filaments. At this high degree of muscle stretch, however, a great number of cross-linkages is necessary to overcome the passive tension and only few cross-linkages are available for shortening. Therefore, in isotonic contractions the amount of shortening is diminished and the time to peak of contraction is augmented with elevated resting tension exceeding 1000 dynes/mm².     

Active,passive and myogenic characteristics of isolated rat intramural coronary resistance arteries

We have investigated the active, passive and myogenic tension-internal circumference relations of rat intramural coronary and, as controls, mesenteric small arteries (internal diameter ca. 200 m) using an isometric myograph. The active tensions of the vessels (when fully activated with 30 M serotonin in K-saline) reached a maximum (2.54 N/m, coronary; 3.39 N/m, mesenteric) at an internal circumference, L₀, where the passive tensions (measured in Ca-free solution) were 0.80 N/m (coronary) and 0.74 N/m (mesenteric). Below 0.8 L₀ and above 1.2 L₀ the active tensions fell linearly, the zero tension intercepts being 0.37 L₀ and 1.74 L₀ (coronary) and 0.40 L₀ and 1.72 L₀ (mesenteric). The passive wall tensions of the vessels rose exponentially as a function of internal circumference, the wall tension at 1.5 L₀ being 10.0 N/m (coronary) and 8.5 N/m (mesenteric). In normal physiological salt solution, the coronary vessels had a Ca²⁺ dependent myogenic tone which was also dependent on the internal circumference. Maximum myogenic tone (0.54 N/m) was obtained at 1.18 L₀. The mesenteric vessels had no such myogenic tone. Histological examination showed that the media/lumen ratios of both vessel types were the same, and that the smooth muscle content of the media was greater in the coronary (81%) than in the mesenteric (72%) vessels. The smaller active tension of the coronary vessels could not therefore be ascribed to a reduced smooth muscle content, but possibly in part to an observed heterogeneous arrangement of the smooth muscle cells in the coronary vessels.     

Frequency dynamics of arterial autoregulation

In anesthetized dogs the low-frequency input impedances (0.001 to 0.1 Hz) of different arterial beds were measured. The following arteries were perfused with blood by a servocontrolled pump in different experiments: Femoral, renal, superior mesenteric, and circumflex branch of the left coronary artery. Step and sinusoidal flow changes were used as input patterns. Furthermore, in the femoral artery the high-frequency input impedance was calculated from pulsatile pressure and flow. The pressure reactions to flow changes were interpreted by assuming a lead-lag autoregulatory control system consisting of two opposing components. The time constants of the two components were found to have characteristic values in different arterial beds and may vary depending on the condition of the experiment. The magnitude of the response usually depends on the mean perfusion pressure, indicating a nonlinear behaviour of the system. Furthermore in the renal artery a characteristic delayed pressure increase was observed after short flow impulses. It is interesting to compare the general pattern of the pressure reaction to the input flow with the force response to stretch which, according to the literature, can be observed in certain striated muscle preparations. The mechanisms underlying the autoregulatory reactions described in this study appear to be, at least in part, a general feature of contractile tissues.     

Elastic Behavior of Porcine Coronary Artery Tissue Under Uniaxial and Equibiaxial Tension

The aim of this study was to characterize the nonlinear anisotropic elastic behavior of healthy porcine coronary arteries under uniaxial and equibiaxial tension. Porcine coronary tissue was chosen for its availability and similarity to human arterial tissue. A biaxial test device previously used to test human femoral arterial tissue samples (Prendergast, P. J., C. Lally, S. Daly, A. J. Reid, T. C. Lee, D. Quinn, and F. Dolan. ASME J. Biomech. Eng., Vol. 125, pp. 692-699, 2003) was further developed to test porcine coronary tissue specimens. The device applies an equal force to the four sides of a square specimen and therefore creates a biaxial stretch that demonstrates the anisotropy of arterial tissue. The nonlinear elastic behavior was marked in both uniaxial and biaxial tests. The tissue demonstrated higher stiffness in the circumferential direction in four out of eight cases subjected to biaxial tension. Even though anisotropy is demonstrated it is proposed that an isotropic hyperelastic model may adequately represent the properties of an artery, provided that an axial stretch is applied to the vessel to simulate the in vivo longitudinal tethering on the vessel. Isotropic hyperelastic models based on the Mooney-Rivlin constitutive equation were derived from the test data by averaging the longitudinal and circumferential equibiaxial data. Three different hyperelastic models were established to represent the test specimens that exhibited a high stiffness, an average stiffness, and a low stiffness response; these three models allow the analyst to account for the variability in the arterial tissue mechanical properties. These models, which take account of the nonlinear elastic behavior of coronary tissue, may be implemented in finite element models and used to carry out preclinical tests of intravascular devices. The errors associated with the hyperelastic models when fitting to both the uniaxial and equibiaxial data for the low stiffness, average stiffness, and high stiffness models were found to be 0.836, 5.206, and 2.980, respectively.     

The relationship of hormones to arterial glycosaminoglycans and atherosclerosis

Glycosaminoglycan fractions were measured in representative large and medium sized arteries of normal, hypophysectomized and hormone treated young beagles. Hyaluronate, heparan sulphate, dermatan sulphate and the isomeric chondroitin sulphates were determined in the aortic arch, thoracic and abdominal segments, in the external iliac, superior mesenteric, renal, common carotid and coronary arteries. The hormones used for replacement therapy of hypophysectomized animals were growth hormone, thyroxine, cortisone and the sex hormones testosterone, estrogen and progesterone. The sensitivity to an individual hormone was found to differ in various segments of the arterial tree; the thoracic and abdominal aorta were most responsive but renal and superior mesenteric arteries were relatively inert. The hypothesis is advanced that arteries with a GAG metabolism highly sensitive to hormones are more prone to develop athero-sclerosis than arteries that have a limited sensitivity to alterations in endocrine balance.     

Effect of Substance P on Various Vascular Beds in the Dog

Using the electromagnetic flowmeter technique, the blood flow in the aorta, carotid, hepatic, superior mesenteric, renal and femoral arteries and portal vein was recorded during continuous i.v. infusion of synthetic Substance P (SP) in 8 dogs. Systemic and portal blood pressures were recorded. A significant decrease in mean arterial blood pressure was recorded at infusion of SP in the femoral vein at a rate of 2.5 ng × min^-1× kg b.w.^-1 or higher. Portal venous blood pressure increased. A rapid increase in the carotid, hepatic, mesenteric and portal blood flow was obtained at infusion rates of 1.2 ng × min^-1× kg b.w.^-1 or higher. The femoral artery responded with a late, transient increase in flow, with a return to the base level while the infusion was still in progress. The renal artery blood flow decreased slightly at low infusion rates and increased at higher. At SP infusions in the portal vein the infusion rate had to be increased to 20 ng × min^-1× kg b.w.^-1 or higher before any general vascular reactions were recorded, indicating that the liver has a high capacity for inactivating SP.     

The Influence of Erythropoietin on the Vascular Responses of Rat Resistance Arteries

This study examined the effect of erythropoietin (EPO) on resting tension and on the responses of rat mesenteric and renal arcuate arteries in vitro to a number of agonists as a possible cause of its blood pressure elevating properties when used therapeutically. Noradrenaline and potassium chloride induced concentration-dependent vasoconstrictions in both vessel types but the basal tension, maximum tension, and the -log concentration producing half-maximal response (pEC50) were altered in the presence of 0.1 or 20 U ml-1 EPO. The thromboxane A2 receptor agonist U46619 induced a constriction of the renal arcuate arteries which was enhanced by EPO at 20 U ml-1, from 1.68 +/- 0.34 to 2.64 +/- 0.39 mN mm-1 (P < 0.01), but which was unchanged by NG-nitro-L-arginine methyl ester (10-4 m). Serotonin (10-9-10-5 M) caused a concentration-related vasoconstriction in renal arcuate arteries which was shifted to the right in the time control study (P < 0.001) but this was abolished by both 0.1 and 20 U ml-1 of EPO. Acetylcholine induced a relaxation of precontracted mesenteric arteries, by 95.4 +/- 1.64 % with an EC50 of 7.08 +/- 0.08 M which was reduced (P < 0.001) by 20 U ml-1 EPO to 81.7 +/- 3.56 % and 6.10 +/- 0.11 M, respectively. The sodium nitroprusside-induced relaxations were unaffected by EPO. The acetylcholine-mediated relaxations in renal arcuate arteries were unchanged by EPO. Bradykinin-induced relaxations in mesenteric and renal arcuate arteries were unaffected by both EPO concentrations. Together these data showed that EPO over a large concentration range had only minor effects on basal tension and the vascular responsiveness of both mesenteric and renal arcuate arteries. The mechanism whereby EPO causes a chronic elevation in blood pressure is unlikely to be due to acute interactions with agonist-mediated responses.     

The cerebral basal arterial network: morphometry of inflow and outflow components

The aim of this project was to study how the morphology of the incoming and outgoing arterial components of the cerebral basal arterial network influence the blood flow to the brain. The cerebral basal arterial network consists of the circulus arteriosus cerebri anteriorly and the basilar artery posteriorly. Diameters of inflow vessels (bilateral vertebral and internal carotid arteries), connecting vessels (anterior communicating, basilar and bilateral posterior communicating arteries) and outflow vessels (anterior, middle and posterior cerebral arteries) were measured and cross‐sectional areas calculated in 51 cadaveric brain specimens. The individual and the average cross‐sectional areas of inflow arteries (51.43 mm²) were significantly bigger than the major outflow arteries (37.76 mm²) but smaller than the combined cross‐sectional areas of outflow (37.76 mm²) and connecting (25.33 mm²) arteries. The difference in the size of arterial cross‐sectional area and the presence of the connecting arteries in the cerebral basal arterial network provides a mechanism for lowering peaks in pressure, and demonstrates a function of the cerebral basal arterial network.     

Regional differences in endothelium-dependent relaxation in the rat: contribution of nitric oxide and nitric oxide-independent mechanisms

Relaxant effects of acetylcholine (ACh), histamine, calcitonin gene-related peptide (CGRP) and the calcium ionophore A23187 were examined in rat femoral (Ø ? 0.2 mm), mesenteric (0.2 mm), intrarenal (0.2 mm) and hepatic (0.3 mm) arteries, and aorta (2 mm). Acetylcholine elicited an endothelium-dependent relaxation in all arteries. Histamine induced an endothelium-dependent relaxation in aorta, and mesenteric and intrarenal arteries, whereas a partly endothelium-dependent and mainly endothelium-independent relaxation was observed in hepatic and femoral arteries, respectively. In hepatic, mesenteric and intrarenal arteries, CGRP induced an endothelium-independent relaxation, whereas either small or no relaxation was obtained in aorta and femoral arteries respectively. A23187 induced an endothelium-dependent relaxation in the aorta and hepatic artery, whereas A23187 had no relaxant effect in femoral, mesenteric and intrarenal arteries. Nω-nitro-l -arginine (l -NOARG, 0.3 mM) reduced the maximum ACh-induced relaxation (in the presence of 10 μM indomethacin) by 66% in the aorta, and abolished the relaxation in femoral and intrarenal arteries. A marked l -NOARG/indomethacin-resistant relaxation was obtained in mesenteric and hepatic arteries. Levcromakalim induced a concentration-dependent and almost complete relaxation in all arteries. When contracted by a 60 mM K⁺ solution, all arteries responded to ACh with a relaxation that was abolished by l -NOARG. These results demonstrate marked regional differences with regard to the vascular effects of ACh, histamine, CGRP and A23187. Whereas nitric oxide appears to mediate endothelium- dependent relaxation regardless of the vascular region, an l -NOARG/indomethacin-resistant relaxation, presumably mediated by an endothelium-derived hyperpolarizing factor, was observed only in mesenteric and hepatic arteries, and aorta.     

Contractions in normal and atherosclerotic rabbit aortas

Length-tension relationships and contractile responses to agonists associated with cyclic nucleotide levels in aortas from atherosclerotic rabbits were studied. The same number of tissues from healthy rabbits was also studied. Diffuse lesions were produced by denudation of the vascular endothelium of rabbit aorta using a balloon catheter and then feeding these rabbits a high cholesterol diet for two months. Stretch-passive tension curves and length-active tension curves which developed in the presence of 60 mM KCl significantly shifted to the left. The altered length-tension relationships indicate a decreased distensibility in these strips and this is attributed to an enhanced accumulation of collagen. Dose-response curve analysis revealed a marked hypersensitivity to serotonin as indicated by greater pD2 values (negative logarithm of half maximum dose) than seen in the controls. In addition, the mean absolute values of the maximum contraction induced by serotonin and KCl were significantly higher than in the controls. Although cyclic AMP levels in the strips with a pathology were lower and cyclic GMP/cyclic AMP ratios were higher than the controls in the basal state, serotonin induced no marked alterations in the cyclic nucleotides levels in the strips from either the diseased or control rabbits. These mechanical and pharmacological alterations of atherosclerotic vessels may relate to clinical events such as coronary spasm.     

Divergent effects of serotonin on coronary-artery dimensions and blood flow in patients with coronary atherosclerosis and control patients

BACKGROUND. Studies in animals have shown that serotonin constricts coronary arteries if the endothelium is damaged, but in vitro studies have revealed a vasodilating effect on isolated coronary segments with an intact endothelium. To investigate the effect of serotonin in humans, we studied coronary-artery cross-sectional area and blood flow before and after the infusion of serotonin in seven patients with angiographically normal coronary arteries and in seven with coronary artery disease. METHODS. We measured the cross-sectional area of the coronary artery by quantitative angiography and coronary blood flow with an intracoronary Doppler catheter. Measurements were obtained at base line and during intracoronary infusions of serotonin (0.1, 1, and 10 micrograms per kilogram of body weight per minute, for two minutes). We repeated the measurements after an infusion of ketanserin, an antagonist of serotonin receptors that is thought to block the effect of serotonin on receptors in the arterial wall but not in the endothelium. RESULTS. In patients with normal coronary arteries, the highest dose of serotonin increased cross-sectional area by 52 percent (P less than 0.001) and blood flow by 58 percent (P less than 0.01). The effect was significantly potentiated by administration of ketanserin. In patients with coronary-artery atherosclerosis, serotonin reduced cross-sectional area by 64 percent (P less than 0.001) and blood flow by 59 percent (P less than 0.001). Ketanserin prevented this effect. CONCLUSIONS. Serotonin has a vasodilating effect on normal human coronary arteries; when the endothelium is damaged, as in coronary artery disease, serotonin has a direct, unopposed vasoconstricting effect. When considered with other evidence, these data suggest that platelet-derived factors such as serotonin may have a role in certain acute coronary ischemic syndromes.     

Determination of an optimal axial-length tension for the study of isolated resistance arteries on a pressure myograph

The effects of longitudinal stretch on vasoreactivity were assessed in isolated, pressurised arteries from the rat mesentery, rat mid-cerebral and human subcutaneous vascular beds. A stretch-dependent increase in reactivity was observed only in rat third order mesenteric arteries. Longitudinal stretch > 20 % (force equal to 0.23 +/- 0.04 mN) optimises vasoconstrictor responses to noradrenaline and phenylephrine in rat third order mesenteric arteries. Stretch did not affect the vasoconstriction response to depolarisation by 30 mM K+ PSS in any of the arteries studied. Similarly, stretch had no affect on pressure-dependent myogenic responses in rat mid-cerebral arteries. Endothelium-independent and endothelium-dependent mechanisms of vasorelaxation were unaffected by stretch in rat third order mesenteric arteries. Likewise, stretch did not affect vasoreactivity in rat mid-cerebral and human subcutaneous resistance arteries. Our results show that longitudinal stretch in isobaric-mounted rat third order mesenteric arteries is an important methodological consideration. Considering our results, we recommend that isobaric-mounted rat third order mesenteric arteries are stretched > 20 % to provide optimal experimental conditions for pharmacological studies.     

不同轴向伸长率下兔股动、静脉的顺应性变化

研究轴向应变对血管顺应性的影响 ,明确能否通过调节吻合张力建立顺应性一致的静脉移植修复动脉缺损模型。取一段做完轴向拉伸实验的血管 (兔股动、静脉分别为 13、12条 ) ,测量不同伸长率下的压力—容积曲线 ,换算为压力—标准容积曲线 ,用幂函数 P=M1 × [еM2 ( v- v0 ) - 1]进行拟合 ,用多项式 M=a1 λ5+a2 λ4 +a3λ3+aλ2 +a5λ+a6 拟合 M- λ数据。由 P=M1 × [еM2 ( v- v0 ) - 1]得出在动脉平均压 (11.78KPa)下血管顺应性 dv/ dp=1/ (M1 ×M2 +11.78M2 )。由张力 T与伸长率 λ的单值对应关系建立起 T与顺应性 dv/ dp的单值对应关系 ,发现在张力 1.19g时 ,在动脉平均压下 ,动静脉的顺应性一致 ,为 0 .0 31,其所对应的动静脉伸长率为 :1.6 7及 1.32     

肾血管性高血压时脑与肠系膜动脉壁CGRP能神经纤维分布的变化

目的：观察肾血管性高血压时中枢与外周动脉壁CGRP（calcitonin gene-related peptide）能神经纤维分布的变化,探讨CGRP与肾血管性高血压的关系.方法：应用免疫组织化学SABC法观察双肾双夹肾血管性高血压大鼠不同时期（术后4、8、12周）脑动脉壁和肠系膜动脉壁CGRP能神经纤维密度的变化.结果：高血压各组CGRP能神经纤维密度均高于对照组,有显著性差异（P＜0.01）;高血压组12周CGRP能神经纤维密度高于高血压组4周,有显著性差异（P＜0.01）;对照组CGRP能神经纤维较纤细,多沿血管长轴走行,高血压组CGRP能神经纤维较粗大,呈网状分布.结论：随着血压的升高,中枢与外周动脉壁CGRP能神经纤维密度增加,这可能是机体产生的一种代偿性保护机制,起着调节血压的作用.     

Relaxant responses to transmural stimulation and nicotine of dog and monkey cerebral arteries

In helical strips of dog and monkey cerebral arteries contracted with prostaglandin F2 alpha, transmural stimulation and nicotine produced relaxations that were abolished by tetrodotoxin and hexamethonium, respectively. These responses were attenuated by quinidine, whereas relaxations of dog coronary arteries to transmural stimulation and isoproterenol were unaffected. Treatment with vasoactive intestinal polypeptide (VIP) and substance P (SP) abolished the relaxant response of cerebral arteries to repeated applications of VIP and SP, respectively; however, after VIP or SP, a normal relaxant response to transmural stimulation or nicotine was produced. Aminophylline suppressed relaxations induced by ATP but not by nerve stimulation. VIP, SP, and adenosine 5'-triphosphate (ATP) relaxed dog cerebral arteries; the responses were unaffected by quinidine. However, only VIP and ATP relaxed monkey cerebral arteries, and SP contracted the arteries. Acetylcholine contracted monkey arteries, in which transmural stimulation produced a relaxation. It may be concluded that nerves innervating the cerebrospinal wall are stimulated electrically and chemically by nicotine, resulting in the arterial relaxation. However, a vasodilator transmitter was not identified. Quinidine appears to selectively antagonize the action of the transmitters on cerebroarterial smooth muscle.