Dimensions and wall force development capacity of human pial arteries from normotensives is not altered in obesity.

OBJECTIVE: The dimensions and maximum wall tension capacity of segments of human pial arteries from normotensive obese and non-obese patients were compared. DESIGN: Segment size was assessed by quantitative morphometry of fixed sections and wall force by in vitro myography. SUBJECTS: Twenty normotensive non-obese and 13 normotensive obese humans body mass index (BMI) 22.4+/-0.5 and 33.9+/-1.7 kg/m(2), respectively) were studied. RESULTS: There was no significant difference in the perimeter of the outer medial border, the smoothed out length of the internal elastic lamina, the ratios of media thickness to area and lumen diameter and the maximum wall force development between the two groups. CONCLUSION: Obesity per se is not associated with initial dimensional changes nor capacity to develop wall tension that might lead to the emergence of hypertension.

As human pial arteries (internal diameter 200-1000 microm) get smaller, their wall thickness and capacity to develop tension relative to their diameter increase.

Pial arteries play a key role in the regulation of human cerebral blood flow. However, many of the features and mechanisms that regulate the tone and diameters of these vessels cannot be studied in situ. One approach is to study in vitro segments of arteries obtained during neurosurgical procedures. The ratios of arterial media thickness to lumen diameter and of the capacity to develop wall force to lumen diameter have important functional consequences and are known to change in disease. Experiments were carried out on pial arteries from normotensive humans to determine the way in which these parameters vary with vessel size. Vessel dimensions--media thickness and lumen diameter were derived from fixed sections using quantitative morphometry. Wall force was measured using a resistance artery myograph. The ratio of media thickness to lumen diameter and of maximum tension developed to lumen diameter both increased as vessel diameter decreased. These ratios do not change over the age range of 15-75 years. These findings show that although in vivo intralumenal pressure falls as human pial arteries become smaller, their media thickness and capacity to develop tone increase.

Functional changes in human pial arteries (300 to 900 micrometer ID) within 48 hours of aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Animal studies of cerebral arteries 2 to 3 days after experimental subarachnoid hemorrhage (SAH) provide evidence of arterial change such as hyperresponsiveness to contractile agonists. There is evidence that small arteries, as well as those large enough to be seen on angiography, may be involved. To directly test these possibilities, the contractile and dilator responses of pial artery segments taken from patients up to 48 hours after SAH were compared with those from patients having elective surgery for an aneurysm (Clip) and with those from normal brain vessels overlying tumors (controls). METHODS: Segments were mounted on a resistance artery myograph for measurements of wall force changes. RESULTS: There were no differences in maximum contractility (Emax) of the 3 groups of segments. The responses of the SAH segments to K+ (30 mmol/L) were 60.7+/-4.6% of Emax (n [number of vessels]=18), which was significantly greater than those of controls (29.9+/-5% Emax) (n=20). Clip responses were the same as control. Contractions of SAH segments to norepinephrine (1 micromol/L) were 54.3+/-7.9% Emax (n=12), and these were significantly greater than those of controls (15.1+/-6.2% Emax) (n=25). All SAH segments showed spontaneous contractile activity of varying patterns. Spontaneous activity did not occur in the Clip group and occurred in only 50% of control segments. Dilation to acetylcholine was numerically less in SAH and Clip segments than in controls, but differences were not statistically significant. The change in agonist responsiveness could result from exposure to agents that damage the blood vessel wall, resulting in partial depolarization of endothelial and smooth muscle cells. CONCLUSIONS: Small human pial arteries are hyperresponsive to contractile agents and show spontaneous contractile activity within 48 hours of SAH. Such effects could result in narrowed resistance arteries and reduction in cerebral blood flow. These effects emphasize the wisdom of early therapeutic intervention.

Intrinsic tone of cerebral artery segments of human infants between 23 weeks of gestation and term.

Segments of basilar and middle cerebral arteries of eight human preterm and early postnatal infants have been examined using the resistance artery myograph technique for wire-mounted segments and the pressure perfusion arteriograph. Myograph-mounted segments spontaneously developed tone of varying duration and time course. Perfused segments showed maintained tone levels of approximately 40% of maximum possible constriction when the intraluminal pressure was 60 mm Hg. This level is not different from that found in adult human pial arteries of similar lumen diameter. Indomethacin (10[-5] M) either initiated tone increase or potentiated existing tone in the isometrically mounted segments. After washout of vasoconstrictors norepinephrine (10[-6] M) and angiotensin II (10[-8] M), indomethacin caused a pronounced, long lasting increase in basal tone. Spontaneous tone was reversed by acetylcholine (10[-6] M), isoproterenol (10[-8] to 10[-5] M), histamine (10[-8] to 10[-5] M), and papaverine (10[-5] M). Low levels of tone were increased and higher levels decreased by intraluminal flow. The pressure/diameter curves of these vessels were of similar shape as those of the equivalent size in the adult. It is concluded that intrinsic tone is a prominent feature of these large cerebral arteries, and it is modified by an endogenous indomethacin-sensitive process.

Weakness of sympathetic neural control of human pial compared with superficial temporal arteries reflects low innervation density and poor sympathetic responsiveness.

BACKGROUND AND PURPOSE: The primary goal of these studies was to understand and investigate the capacity of perivascular nerves to influence the tone of human pial arteries and to compare them with other human cephalic arteries, the superficial temporal and middle meningeal. METHODS: Responses to electrical activation of intramural nerves and related features of fresh segments of human cephalic arteries-the pial (PA; 478+/-34 microm ID), middle meningeal (MMA; 540+/-41 microm ID), and superficial temporal (STA; 639+/-49 microm ID)-obtained from patients aged 15 to 82 years during surgical procedures were studied on a resistance artery myograph. RESULTS: The PA segment responses to electrical nerve activation and to norepinephrine (NE; 10[-5] mol/L) were 1% and 21% of tissue maximum, respectively, compared with 6% and 34% for the MMA and 14% and 90% for the STA. Tissue maximum was defined as the force increase to 127 mmol/L KCl plus arginine vasopressin (1 microm). All arteries dilated well to acetylcholine. Possible explanations for the PA marginal neurogenic responses were assessed. NE ED50 was 5.4+/-2.2 X 10(-7) mol/L and did not vary with age or diameter. NE responsiveness did not increase in vessels with spontaneous or raised potassium-induced tone. Relaxation to isoproterenol was variable and propranolol did not increase the neurogenic response. Neither N(G)-monomethyl-L-arginine, N(G)-nitro-L-arginine methyl ester, endothelium removal, nor indomethacin consistently influenced the contractions to NE or neurogenic reactivity. The weak PA neurogenic response is in keeping with its poor innervation. As determined by catecholamine histofluorescence, innervation in the PA is sparse, with density increasing in the order PA, MMA, and STA. The incidence of nerve structures in the PA adventitio-medial junction was only 3% of those in the STA, and these were situated more than 3 microm from the closest smooth muscle cell. CONCLUSIONS: We conclude that the weak neurogenic response of adult human pial artery reflects its poor innervation and responsiveness to NE, implying that these features are not important in the regulation of its diameter.

Diameter dependence of myogenic tone of human pial arteries. Possible relation to distensibility.

BACKGROUND AND PURPOSE: Responses to changes in intraluminal pressure of isolated human pial arteries (200 to 1200 microns i.d.) obtained from patients undergoing neurosurgery were measured. METHODS: The vessels were cannulated and pressurized (60 mm Hg); vascular diameter and intraluminal pressure were recorded simultaneously. After spontaneous development of steady state tone, intraluminal pressure was changed to both higher and lower levels in random sequence. RESULTS: Human pial arteries exhibited myogenic responses and maintained their diameter over the pressure range of 20 to 100 mm Hg. The level of myogenic tone observed at 30 mm Hg did not vary significantly with artery diameter. In contrast, at 60 and 90 mm Hg, the extent of myogenic tone increased as the diameter decreased (up to 70% to 80% of maximum in 200-microns i.d. arteries). The arteries contracted to KCl 30 mmol/L, norepinephrine 1 mumol/L, and vasopressin 0.1 mumol/L and relaxed to acetylcholine 3 mumol/L. The extent of these responses did not vary with the diameter of the artery. Arterial distensibility, represented by the slope of the tangent of the passive pressure-diameter curve at lower pressures (5 to 50 mm Hg), increased as arteries became smaller. This is consistent with the possibility that the level of myogenic tone is related to vessel distensibility. Human omental arteries of comparable size did not develop myogenic tone but contracted to KCl and norepinephrine and relaxed to acetylcholine to an extent similar to pial arteries. CONCLUSIONS: There is a specific gradient of myogenic responsiveness in human pial arteries that varies inversely with their diameter. This tone does not develop in all vascular beds. These levels of tone in the pial circulation would be expected to be of profound functional significance by allowing blood flow to vary widely.

Role of Ca(2+)-activated K+ channels in the regulation of membrane potential and tone of smooth muscle in human pial arteries.

Smooth muscle cells (SMCs) in 58% of human pial arteries obtained during surgery showed no spontaneous contractions and displayed a stable resting membrane potential (MP) of -54.7 +/- 1.5 mV. Those that exhibited periodic spontaneous contractions associated with periodic depolarization and generation of spontaneous action potentials (APs) had a less negative MP of -43.1 +/- 0.5 mV (42%). Inhibition of calcium-activated potassium (KCa) channels in the silent arteries by charybdotoxin (CTX) and tetraethylammonium ions (TEA) induced dose-dependent depolarization, AP generation, and contraction. TEA and CTX enhanced the spontaneous depolarization and force in arteries that exhibited spontaneous activity. They also prolonged the spontaneous APs up to several times and increased their upstroke amplitude. Both TEA and CTX failed to produce significant depolarization in arteries treated with nifedipine. It is concluded that KCa channels are important regulators of human pial artery SMC resting MP and tone. They are also involved in the control of AP amplitude and duration and the associated contractions. These data suggest that alterations in the activity of SMC KCa channels could be responsible for the appearance of spontaneous activity in human pial arteries in vitro and that impaired function of these channels might be related to vasospastic phenomena in human cerebral circulation.

Electrical activity underlying rhythmic contraction in human pial arteries.

Human pial arteries obtained during surgery frequently exhibit spontaneous periodic contractions. Simultaneous measurements of membrane potential and vessel wall force were used to examine whether these contractions are associated with electrical activity of smooth muscle cells (SMCs). A total of 53 segments from 38 patients were studied, and of these, 26 showed spontaneous contractions related to periodic depolarization and generation of action potentials (APs). The resting membrane potential during the silent periods was -44.0 +/- 0.5 mV. APs without "overshoot'' were observed when spontaneous depolarization reached levels of -40 to -35 mV. Just over half of the arterial segments failed to exhibit spontaneous activity; however, APs could be generated during K+-induced depolarization. The mean SMC resting membrane potential of these vessels was -53.5 +/- 1.5 mV, and this value differed significantly from that of SMCs in spontaneously active arteries. Application of tetrodotoxin did not change the amplitude and duration of APs. Removal of Ca2+ from the bathing solution and addition of nifedipine completely inhibited the spontaneous APs and associated contractions. K+ depolarization failed to induce APs and contraction in the presence of nifedipine. We conclude that periodic spontaneous depolarization and AP generation underlie the periodic spontaneous contractions of human pial arteries. Both the APs and associated contractions are related to the activation of dihydropyridine-sensitive voltage-dependent Ca2+ channels. It is suggested that AP generation can be responsible for vasomotion of human pial arteries in vivo.

Comparison of density of sympathetic varicosities and their closeness to smooth muscle cells in rabbit middle cerebral and ear arteries and their branches.

The density and nerve varicosity-smooth muscle cell separation of rabbit cerebral and ear arterial beds were compared. The rabbit middle cerebral artery and three of its successive branches and a comparable-sized ear artery and two branches were perfusion-fixed for electron microscopy and analyzed by quantitative morphometric procedures. The purpose was to determine if there are structural correlates to previously observed differences in the sympathetic control of these two vascular systems. The in vitro contractile response of isolated artery segments to electrical field stimulation of their intramural nerves is considerably less in cerebral arteries compared with the similar-sized ear arteries. Furthermore, in the cerebral but not the ear circulation, there is progressive diminution of the neurogenic response with successive branching. Although the total varicosity densities of the major ear and brain arteries studied are similar, and this parameter stays fairly constant with successive branching of the ear, it falls off considerably in the cerebral vessels. There is a significant difference in densities between the two vascular beds when "bare" varicosities located < 1 micron from the medial smooth muscle are compared. The second-order branch of the ear artery has an average of 18 bare varicosities per 500-micron circumference, and the corresponding cerebral vessel has only 2.8 bare varicosities per 500-micron circumference. The mean bare varicosity-smooth muscle cell separation (mean +/- SEM) is significantly (P < .05) less in the ear (1.18 +/- 0.06 microns) than in the cerebral arteries (4.95 +/- 0.23 microns). This is true of all vessels studied. Fifty-nine percent of the bare varicosities in the ear arteries are < 1 micron from the smooth muscle cells, and 1.2% are more distant than 5 microns. These values for cerebral vessels are 9.5% and 37%, respectively. In the ear vessels, 25% of the bare varicosities make close neuromuscular contact (within 500 nm of the smooth muscle), whereas only 3% do so in cerebral vessels; in cerebral compared with ear vessels, the percentage becomes significantly less with branching. These structural features of brain vessels, taken together with the lower sensitivity to and the diminished capacity to respond to norepinephrine, probably account for their weak neurogenic control. The results indicate that the cerebral circulation of the rabbit receives a sympathetic innervation that is relatively ineffective in altering cerebrovascular tone.

Sympathetic denervation of resistance arteries increases contraction and decreases relaxation to flow.

The effect of chronic sympathetic and possibly sensory denervation on flow-induced changes in smooth muscle tone was examined in a branch of the rabbit ear artery (200-400 microns ID). The superior cervical ganglion and 1-cm portions of the greater and anterior auricular nerves were removed from 4-wk-old rabbits while under general anesthesia, and arterial segments were studied 21 days later. Efficacy of denervation was assessed by catecholamine histochemistry and by absence of a constrictor response to transmural electrical field stimulation. Intraluminal flow of physiological saline solution was made through a pipette into matched-innervated and -denervated segments. Flow-induced contraction was increased in the denervated compared with the contralateral innervated segments. At the lowest flow rate studied (1 microliters/min), the contraction increased more than six times. This is consistent with the previously described nonspecific, nondeviational hypersensitivity of denervated vascular smooth muscle to constrictor influences. By contrast flow-related dilation at 10 and 20 microliters/min was significantly diminished. An intraluminal flow rate could be found that resulted in dilation in innervated but not the matched-denervated segments. Endothelial-mediated dilation to acetylcholine was also impaired. Chronic sympathetic denervation increased the magnitude of flow contraction and decreased that of flow relaxation.

Vascular alpha-adrenoceptor affinity variation is not due to varying populations of subtypes distinguished by WB 4101 and chlorethylclonidine.

Interaction with chlorethylclonidine has been used to subdivide populations of alpha 1-adrenoceptors in some tissues. WB 4101 can distinguish high and low affinity states of the receptor. The present study was carried out to determine if different populations or affinity states of alpha 1-adrenoceptors distinguished by either of these compounds, could explain the variation in alpha 1-adrenoceptor agonist affinity found amongst rabbit arteries. Five arteries were studied whose affinity for noradrenaline vary between 4.8 and 6.4. These were the thoracic aorta, renal, superior mesenteric, ear and ovarian arteries. WB 4101 was found to be equally effective in antagonizing noradrenaline on all arteries. Chlorethylclonidine caused a 20-fold rightward shift of the noradrenaline dose-contraction curve in the thoracic aorta; but had little or no effect on the other vessels. Thus, the combination of different proportions of subsets of alpha 1-adrenoceptors distinguished by WB 4101 or chlorethylclonidine does not explain the variation in alpha 1-adrenoceptor affinity found in these rabbit arteries.

Clentiazem protects against chronic cerebral vasospasm in rabbit basilar artery.

BACKGROUND AND PURPOSE: Experiments were carried out in rabbits to determine whether clentiazem (8-chlorodiltiazem), a cerebrovascular-selective calcium channel blocker, administered 24 hours before subarachnoid hemorrhage influenced the subsequent cerebral vasospasm. METHODS: Subarachnoid hemorrhage was induced by multiple injections of blood into the prepontine cisterns of 35 male New Zealand White rabbits, and clentiazem (5 mg/kg) was administered 4 times daily until sacrifice. Cerebral artery diameter was assessed in vivo by angiography. Functional features of basilar arteries were measured using conventional in vitro methodology. RESULTS: Clentiazem reduced the angiographic narrowing seen on days 2 and 5 from 35% and 34%, respectively (sham control, 1.42 +/- 0.31 mm [n = 22]), to 8% and 11%, respectively, and prevented the narrowing (32%) that occurred on day 9. Narrowing in the untreated rabbits was only partly reversed by papaverine; all narrowing in clentiazem-treated animals was papaverine sensitive. Clentiazem prevented or reduced many of the changes in the basilar artery caused by the subarachnoid hemorrhage. Of particular relevance to arterial narrowing were the increased wall stiffness, the transient spontaneous changes in wall force, and the reduction in relaxation to acetylcholine. Reduction of the changes in wall force induced by agonists and by stimulation of intramural sympathetic nerves was observed. CONCLUSIONS: The vascular damage associated with chronic cerebral vasospasm is related to calcium entry into the smooth muscle and endothelial cells, and possibly sympathetic nerve terminals, through calcium channels sensitive to clentiazem, which suggests that clentiazem may be of value in the management of chronic cerebral vasospasm.

Effects of postnatal growth and denervation on characteristics of the saphenous artery in SHR and WKY rats between 3 and 6 weeks of age: an in vitro study.

Thigh vessels of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were unilaterally surgically denervated at 10 days of age by femoral nerve section. Denervated and contralateral control segments of saphenous arteries from 3- and 6-week-old rats were mounted in a small vessel myograph for study. Both strains showed growth changes in blood pressure, but there was no significant difference between WKY and SHR. Both strains also had significant growth changes in vessel dimensions and the in vitro measurements suggested that SHR vessels had a thicker wall. Denervation did not affect vessel size. Transmural nerve stimulation indicated loss of innervation due to the surgical procedure. In the denervated vessels, both norepinephrine (NE) and 5-hydroxytryptamine (5-HT) dose response curves were shifted to the left, indicating a postjunctional increase in sensitivity. Maximum tension developed was in the order K+ greater than 5-HT greater than NE. In comparing the two strains, vessels from 6-week-old SHR were less sensitive to 5-HT. Relaxation to acetylcholine was significantly decreased in denervated arteries from WKY, whereas in SHR the significant decrease occurred only at 3 weeks. Denervated vessels from both rat strains at 3 weeks showed greater relaxation to beta-receptor activation, but not at 6 weeks of age. Therefore, the absence of functional innervation resulted in altered function of the saphenous artery wall.

Longitudinal time course of reversible and irreversible components of chronic cerebrovasospasm of the rabbit basilar artery.

Multiple injections of autologous blood were made around the basilar artery of rabbits through a silicone catheter placed into the prepontine cistern. The total blood injected was 3 ml/kg in aliquots of 0.5 to 0.8 ml over a 4-hour period. Control angiograms were obtained 7 days before this procedure. Groups of animals were examined by angiography on each of 9 days after the injections of blood. An angiogram was obtained 15 minutes after the first injection of blood, 20 seconds after the intra-arterial injection of a maximum dilating dose of papaverine. All surviving animals showed basilar artery narrowing, which was greatest 24 hours after the hemorrhage, when the vessel diameter was reduced to 54% of the control value. The narrowing then decreased to a reduction of about 30%, which was maintained throughout the rest of the study period. A papaverine-resistant component of narrowing was not seen until the 3rd day. It increased progressively to Day 9 when it represented 63% of the total. This model has a number of features that are reminiscent of human cerebrovasospasm, including the fact that there is an initial phase of narrowing that is completely reversed by an intra-arterially administered vasodilator, and a second phase beginning on Day 3 which exhibits a progressively increasing papaverine-resistant component.

Variation in the interaction of some phenylethylamine and imidazoline derivatives with alpha-1 adrenoceptors in rabbit arteries: further evidence for the variable receptor affinity hypothesis.

This study was undertaken to determine whether the variation in the affinity of the alpha-1 adrenoceptors previously found for norepinephrine and phenylephrine in different arteries is also seen with other alpha-1 adrenoceptor agonists, and if so, if one part of the structure is particularly responsible for the variation. The potency and dissociation constants of eight agonists, both phenylethylamines and imidazolines, were determined in five rabbit arteries. In each artery the rank order of phenylethylamine agonist potency was epinephrine greater than norepinephrine greater than phenylephrine greater than deoxyepinephrine greater than methoxamine greater than dopamine. The same rank order of dissociation constants was found. For the imidazolines, the potency order was oxymetazoline greater than clonidine. For each agonist, there was a linear correlation between artery sensitivity and receptor affinity. None of the regression line slopes differed from each other. For each artery there was a linear correlation between phenylethylamine sensitivity and affinity. With the exception of the ovarian, which was lower, slopes of the regression lines in each group do not differ from each other. There were differences in the spread of the dissociation constants of the phenylethylamine derivatives among the arteries. The range of affinities was most marked with norepinephrine (greater than 40-fold) and least with epinephrine (approximately 4-fold). They suggest that agonist affinity governs the biological activity of at least the phenylethylamines on rabbit arteries mediated by the alpha-1 adrenoceptor. Variation in agonist affinity can explain the extent of the biological response. Differences in range of amine affinities in different arteries suggest that the agonist recognition site, although similar in the different arteries, is not identical and may be related particularly to some variation of the amine attachment site of the molecule. The results provide further support for the variable receptor affinity hypothesis.

Longitudinal in vivo and in vitro time-course study of chronic cerebrovasospasm in the rabbit basilar artery.

Subarachnoid hemorrhage (SAH) was induced by multiple injections of autologous blood into the prepontine cistern in the rabbit. Long-lasting angiographic narrowing was recorded over a period of nine days after SAH. Papaverine (PPV) reversed angiographic narrowing in the first three days after SAH. Vasospasm was refractory to PPV from day five to day nine after SAH. PPV - refractoriness (in vivo) was positively correlated with decreased vessel wall distensibility (in vitro). Arterial segments showed spontaneous increases in tone in the first two days after SAH. Other alterations observed include a marked gradual reduction in the capacity of the vessel wall to contract, reduction in constrictor nerve influences on vascular tone, and impaired acetylcholine - induced vasorelaxation. Tonic contraction to the maximum dose of serotonin was increased in acute spasm and decreased in chronic spasm. It is suggested that the initial cause of arterial narrowing after SAH is the action of vasoactive substances released in the close vicinity of the arterial wall; this then leads to abnormal tone, tissue damage, and structural changes.

Variable receptor affinity and tissue sensitivity.

Vascular smooth muscle sensitivity to norepinephrine (NE), measured by contractile responses in vitro, varied in different arteries of the rabbit and also in the same vessels in other species. There was a good correlation between variation in the affinity of NE for the alpha 1-adrenoceptor and tissue sensitivity. The variation was continuous and probably not indicative of different receptor subtypes. Solubilization of alpha 1-adrenoceptors from the membrane changed the affinity for specific ligands while reconstitution restored it. Taken together, these results suggest the presence of a factor(s) within the receptor microenvironment capable of modulating affinity and hence tissue sensitivity to NE. In some blood vessels, receptor number was correlated significantly with affinity of the alpha 1-adrenoceptor for NE also. In general, the contribution of receptor number was considerably less than the affinity for NE.

Two indices of functional damage of the artery wall parallel the time course of irreversible narrowing in experimental vasospasm in the rabbit.

Autologous blood placed around the basilar artery caused angiographic narrowing with a biphasic time course. The first immediate phase was reversed by intraarterial papaverine; the second exhibited an increasing component of narrowing which was papaverine-resistant. In vitro studies showed that vessels became increasingly stiffer, less capable to develop active tone, and less responsive to vasoconstrictors and vasodilators. The papaverine-resistant component of angiographic narrowing (in vivo) could be directly correlated with loss of contractility and increased artery wall stiffness (in vitro).

Pharmacologic irreversible narrowing in chronic cerebrovasospasm in rabbits is associated with functional damage.

We studied isolated basilar artery segments from a rabbit model of chronic cerebrovasospasm. Autologous blood placed around the basilar artery of rabbits killed 1, 2, 3, 4, 5, 6, 7, or 9 days later caused narrowing of the segments with a biphasic time course. The first (immediate) phase was reversed by intra-arterial papaverine; the second phase exhibited an increasing component of narrowing that was papaverine-insensitive. Based on the passive force/length curves, basilar artery segments became increasingly stiff over 9 days. By contrast, the segments' contractility decreased. Responses of the basilar artery segments were greater over the first few days, but then became less than that of saline-injected controls. Contractions in response to norepinephrine and potassium were reduced. Endothelium-based acetylcholine-induced vasodilation progressively diminished, as did the response to sympathetic nerve stimulation. There was a negative correlation between artery wall stiffness and contractility. The papaverine-insensitive component of angiographic narrowing correlated directly with loss of contractility and with artery wall stiffness. These results are consistent with the conclusion that increased artery wall stiffness is a primary determining factor in the arterial narrowing of chronic cerebrovasospasm.

Influence of adrenergic innervation on vascular growth and mature characteristics.

Sympathetic nerve control of systemic and pulmonary vasculatures is discussed. The effect of removal of the nerve influence postnatally and subsequent development of arterial structure and function is contrasted with denervation in the adult, with reference to the rabbit ear and rat mesenteric arterial vasculature. Evidence is given that sympathetic nerves exert a trophic effect on vascular structure and function, particularly during growth that is associated with nerve activity.