Vitamin B6 prevents Isocarbophos-induced posterior cerebral artery injury in offspring rats through up-regulating S1P receptor expression.

We have previously reported that the long-term exposure of Isocarbophos, a kind of organophosphorus compounds, induces vascular dementia (VD) in rats. Studies have also shown that organophosphorus compounds have adverse effects on offsprings. Vitamin B6 is a coenzyme mainly involved in the regulation of metabolism and has been demonstrated to ameliorate VD. Sphingosine-1-phosphate (S1P), a biologically active lipid, plays a vital role in the cardiovascular system. However, whether S1P is involved in the therapeutic effects of Vitamin B6 on posterior cerebral artery injury has yet to be further answered. In the present study, we aimed to explore the potential influence of Vitamin B6 on Isocarbophos-induced posterior cerebral artery injury in offspring rats and the role of the S1P receptor in this process. We found that Vitamin B6 significantly improves the vasoconstriction function of the posterior cerebral artery in rats induced by Isocarbophos by the blood gas analysis and endothelium-dependent relaxation function assay. We further demonstrated that Vitamin B6 alleviates the Isocarbophos-induced elevation of ICAM-1, VCAM-1, IL-1, and IL-6 by using the enzyme-linked immunosorbent assay kits. By performing immunofluorescence and the western blot assay, we revealed that Vitamin B6 prevents the down-regulation of S1P in posterior cerebral artery injury. It is worth noting that Fingolimod, the S1P inhibitor, significantly inhibits the Vitamin B6-induced up-regulation of S1P in posterior cerebral artery injury. Collectively, our data indicate that Vitamin B6 may be a novel drug for the treatment of posterior cerebral artery injury and that S1P may be a drug target for its treatment.

Selective posterior cerebral artery amobarbital test: a predictor of memory following subtemporal selective amygdalohippocampectomy.

BACKGROUND: The selective posterior cerebral artery (PCA) amobarbital test, or PCA Wada test, is used to predict memory impairment after epilepsy surgery in patients who have previously had a failed internal carotid artery (ICA) amobarbital test. METHODS: Medical records from 2012 to 2018 were retrospectively reviewed for all patients with seizures who underwent a selective PCA Wada test at our institution following a failed or inconclusive ICA Wada test. Standardized neuropsychological testing was performed before and during the Wada procedure and postoperatively in patients who underwent resection. RESULTS: Thirty-three patients underwent a selective PCA Wada test, with no complications. Twenty-six patients with medically refractory epilepsy had a seizure focus amenable to selective amygdalohippocampectomy (AHE). Six patients (23%, n=26) had a failed PCA Wada test and did not undergo selective AHE, seven (27%) declined surgical resection, leaving 13 patients who underwent subtemporal selective AHE. Hippocampal sclerosis was found in all 13 patients (100%). Twelve patients (92%) subsequently underwent formal neuropsychological testing and all were found to have stable memory. Ten patients (77%) were seizure-free (Engel Class I), with average follow-up of 13 months. CONCLUSION: The selective PCA Wada test is predictive of memory outcomes after subtemporal selective AHE in patients with a failed or inconclusive ICA Wada test. Furthermore, given the low risk of complications and potential benefit of seizure freedom, a selective PCA Wada test may be warranted in patients with medically intractable epilepsy who are candidates for a selective AHE and who have a prior failed or inconclusive ICA Wada test.

Ischemic Stroke Associated With Calcitonin Gene-Related Peptide Inhibitor Therapy for Migraine: A Case Report.

Calcitonin gene-related peptide (CGRP) is involved in nociception and neurogenic inflammation in migraine, but also serves as a potent vasodilator acting on intracranial arteries. This latter effect raises concern about the possibility of drugs inhibiting CGRP precipitating cerebral ischemia. We describe a 41-year-old woman with migraine without aura who developed a right thalamic infarction following a first dose of erenumab, a CGRP-receptor blocker. Stroke onset occurred during a typical migraine. Imaging demonsrated right posterior cerebral artery near-occlusion initially with normalization of the vessel at follow-up imaging 2 months later, suggesting vasospasm as a possible mechanism. Extensive evaluation revealed no other specific cause of stroke or vascular risk factors aside from long-term use of oral contraceptive pills. CGRP inhibitors might be associated with ischemic stroke due to blockade of normal cerebral vasodilatory regulatory function.

Percheron Infarction: Is It Just a Rare Cerebrovascular Variant or a Forewarning of Severe Multiple Posterior Circulation Infarcts.

Percheron infarction, arising from occlusion of the Artery of Percheron, is few, which can result in bilateral thalamic and mesencephalic infarctions. We herein showcase a confirmed case of the Percheron infarction at the admission day, in which the patient advanced into severe multiple posterior circulation infarcts, along with petechial hemorrhage within the infarcts, even given the right therapy without delay. It reminds us that whether we could or should take this special infarction as a forewarning of more harmful infarcts getting in the way, or at least a precaution of poor vessel condition.

A chronic physical activity treatment in obese rats normalizes the contributions of ET-1 and NO to insulin-mediated posterior cerebral artery vasodilation.

This study tested the hypotheses that obesity-induced decrements in insulin-stimulated cerebrovascular vasodilation would be normalized with acute endothelin-1a receptor antagonism and that treatment with a physical activity intervention restores vasoreactivity to insulin through augmented nitric oxide synthase (NOS)-dependent dilation. Otsuka Long-Evans Tokushima Fatty rats were divided into the following groups: 20 wk old food controlled (CON-20); 20 wk old free food access (model of obesity, OB-20); 40 wk old food controlled (CON-40); 40 wk old free food access (OB-40); and 40 wk old free food access+RUN (RUN-40; wheel-running access from 20 to 40 wk). Rats underwent Barnes maze testing and a euglycemic hyperinsulinemic clamp (EHC). In the 40-wk cohort, cerebellum and hippocampus blood flow (BF) were examined (microsphere infusion). Vasomotor responses (pressurized myography) to insulin were assessed in untreated, endothelin-1a receptor antagonism, and NOS inhibition conditions in posterior cerebral arteries. Insulin-stimulated vasodilation was attenuated in the OB vs. CON and RUN groups (P ≤ 0.04). Dilation to insulin was normalized with endothelin-1a receptor antagonism in the OB groups (between groups, P ≥ 0.56), and insulin-stimulated NOS-mediated dilation was greater in the RUN-40 vs. OB-40 group (P < 0.01). At 40 wk of age, cerebellum BF decreased during EHC in the OB-40 group (P = 0.02) but not CON or RUN groups (P ≥ 0.36). Barnes maze testing revealed increased entry errors and latencies in the RUN-40 vs. CON and OB groups (P < 0.01). These findings indicate that obesity-induced impairments in vasoreactivity to insulin involve increased endothelin-1 and decreased nitric oxide signaling. Chronic spontaneous physical activity, initiated after disease onset, reversed impaired vasodilation to insulin and decreased Barnes maze performance, possibly because of increased exploratory behavior.NEW & NOTEWORTHY The new and noteworthy findings are that 1) in rodents, obesity-related deficits in insulin-mediated vasodilation are associated with increased influence of insulin-stimulated ET-1 and depressed influence of insulin-stimulated NOS and 2) a physical activity intervention, initiated after the onset of disease, restores insulin-mediated vasodilation, likely by normalizing insulin-stimulated ET-1 and NOS balance. These data demonstrate that the treatment effects of chronic exercise on insulin-mediated vasodilation extend beyond active skeletal muscle vasculature and include the cerebrovasculature.

Low dose resveratrol improves cerebrovascular function in type 2 diabetes mellitus.

BACKGROUND AND AIMS: Progressive microvascular dysfunction in type 2 diabetes mellitus (T2DM) may impair the ability of cerebral vessels to supply blood to brain regions during local metabolic demand, thereby increasing risks of dementia. Having previously demonstrated that resveratrol can enhance vasodilator function in the systemic circulation, we hypothesised that resveratrol could similarly benefit the cerebral circulation. We aimed to determine the most efficacious dose of resveratrol to improve cerebral vasodilator responsiveness (CVR) in T2DM. METHODS AND RESULTS: In a double-blind, placebo-controlled, balanced crossover intervention, 36 dementia-free, non-insulin dependent T2DM older adults (49-78 years old) consumed single doses of synthetic trans-resveratrol (0, 75, 150, and 300 mg) at weekly intervals. Transcranial Doppler ultrasound was used to assess CVR to a hypercapnic stimulus, both before and 45 min after treatment. CVR, measured bilaterally in the middle cerebral arteries (MCA) and posterior cerebral arteries (PCA), was expressed as the percentage change in mean blood flow velocity from baseline to the peak velocity attained during hypercapnia. Resveratrol consumption increased CVR in the MCA; mean within-individual changes for each dose from placebo were 13.8 ± 3.5% for 75 mg (P = 0.001), 8.9 ± 3.5% for 150 mg (P = 0.016), and 13.7 ± 3.3% for 300 mg (P < 0.001); only the 75 mg dose was efficacious in the PCA (13.2 ± 4.5%, P = 0.016). CONCLUSIONS: Our results provide the first clinical evidence of an acute enhancement of vasodilator responsiveness in cerebral vessels following consumption of resveratrol in this population who are known to have endothelial dysfunction and sub-clinical cognitive impairment. Importantly, maximum improvement was observed with the lowest dose used. CLINICAL TRIAL REGISTRATION: ACTRN12614000891628 (www.anzctr.org.au).

Chronic administration of isocarbophos induces vascular cognitive impairment in rats.

Vascular dementia, being the most severe form of vascular cognitive impairment (VCI), is caused by cerebrovascular disease. Whether organophosphorus causes VCI remains unknown. Isocarbophos (0.5 mg/kg per 2 days) was intragastrically administrated to rats for 16 weeks. The structure and function of cerebral arteries were assayed. The learning and memory were evaluated by serial tests of step-down, step-through and morris water maze. Long-term administration of isocarbophos reduced the hippocampal acetylcholinesterase (AChE) activity and acetylcholine (ACh) content but did not alter the plasma AChE activity, and significantly damaged the functions of learning and memory. Moreover, isocarbophos remarkably induced endothelial dysfunction in the middle cerebral artery and the expressions of ICAM-1 and VCAM-1 in the posterior cerebral artery. Morphological analysis by light microscopy and electron microscopy indicated disruptions of the hippocampus and vascular wall in the cerebral arteries from isocarbophos-treated rats. Treatment of isocarbophos injured primary neuronal and astroglial cells isolated from rats. Correlation analysis demonstrated that there was a high correlation between vascular function of cerebral artery and hippocampal AChE activity or ACh content in rats. In conclusion, chronic administration of isocarbophos induces impairments of memory and learning, which is possibly related to cerebral vascular dysfunction.

Plasma from patients with HELLP syndrome increases blood-brain barrier permeability.

Circulating inflammatory factors and endothelial dysfunction have been proposed to contribute to the pathophysiology of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. To date, the occurrence of neurological complications in these women has been reported, but few studies have examined whether impairment in blood-brain barrier (BBB) permeability or cerebrovascular reactivity is present in women having HELLP syndrome. We hypothesized that plasma from women with HELLP syndrome causes increased BBB permeability and cerebrovascular dysfunction. Posterior cerebral arteries from female nonpregnant rats were perfused with 20% serum from women with normal pregnancies (n = 5) or women with HELLP syndrome (n = 5), and BBB permeability and vascular reactivity were compared. Plasma from women with HELLP syndrome increased BBB permeability while not changing myogenic tone and reactivity to pressure. Addition of the nitric oxide (NO) synthase inhibitor N(ω)-nitro-L-arginine methyl ester caused constriction of arteries that was not different with the different plasmas nor was dilation to the NO donor sodium nitroprusside different between the 2 groups. However, dilation to the small- and intermediate-conductance, calcium-activated potassium channel activator NS309 was decreased in vessels exposed to HELLP plasma. Thus, increased BBB permeability in response to HELLP plasma was associated with selective endothelial dysfunction.

Perturbed and spontaneous regional cerebral blood flow responses to changes in blood pressure after high-level spinal cord injury: the effect of midodrine.

Individuals with spinal cord injury (SCI) above the T6 spinal segment suffer from orthostatic intolerance. How cerebral blood flow (CBF) responds to orthostatic challenges in SCI is poorly understood. Furthermore, it is unclear how interventions meant to improve orthostatic tolerance in SCI influence CBF. This study aimed to examine 1) the acute regional CBF responses to rapid changes in blood pressure (BP) during orthostatic stress in individuals with SCI and able-bodied (AB) individuals; and 2) the effect of midodrine (alpha1-agonist) on orthostatic tolerance and CBF regulation in SCI. Ten individuals with SCI >T6, and 10 age- and sex-matched AB controls had beat-by-beat BP and middle and posterior cerebral artery blood velocity (MCAv, PCAv, respectively) recorded during a progressive tilt-test to quantify the acute CBF response and orthostatic tolerance. Dynamic MCAv and PCAv to BP relationships were evaluated continuously in the time domain and frequency domain (via transfer function analysis). The SCI group was tested again after administration of 10 mg midodrine to elevate BP. Coherence (i.e., linearity) was elevated in SCI between BP-MCAv and BP-PCAv by 35% and 22%, respectively, compared with AB, whereas SCI BP-PCAv gain (i.e., magnitudinal relationship) was reduced 30% compared with AB (all P < 0.05). The acute (i.e., 0-30 s after tilt) MCAv and PCAv responses were similar between groups. In individuals with SCI, midodrine led to improved PCAv responses 30-60 s following tilt (10 ± 3% vs. 4 ± 2% decline; P < 0.05), and a 59% improvement in orthostatic tolerance (P < 0.01). The vertebrobasilar region may be particularly susceptible to hypoperfusion in SCI, leading to increased orthostatic intolerance.

Cerebrovascular dysfunction and blood-brain barrier permeability induced by oxidized LDL are prevented by apocynin and magnesium sulfate in female rats.

Oxidized low-density lipoprotein (oxLDL) is elevated during several neurologic conditions that involve cerebral edema formation, including severe preeclampsia and eclampsia; however, our understanding of its effect on the cerebral vasculature is limited. We hypothesized that oxLDL induced blood-brain barrier (BBB) disruption and changes in cerebrovascular reactivity occur through NADPH oxidase-derived superoxide. We also investigated the effect of MgSO4 on oxLDL-induced changes in the cerebral vasculature as this is commonly used in preventing cerebral edema formation. Posterior cerebral arteries from female rats were perfused with 5 µg/mL oxLDL in rat serum with or without 50 µM apocynin or 16 mM MgSO4 and BBB permeability and vascular reactivity were compared. oxLDL increased BBB permeability and decreased myogenic tone that were prevented by apocynin. oxLDL increased constriction to the nitric oxide synthase inhibitor nitro-L-arginine that was unaffected by apocynin. oxLDL enhanced dilation to the NO donor sodium nitroprusside that was prevented by apocynin. MgSO4 prevented oxLDL-induced BBB permeability without affecting oxLDL-induced changes in myogenic tone. Thus, oxLDL seems to cause BBB disruption and vascular tone dysregulation through NADPH oxidase-derived superoxide. These results highlight oxLDL and NADPH oxidase as potentially important therapeutic targets in neurologic conditions that involve elevated oxLDL.

The role of sphingosine kinase 1/sphingosine-1-phosphate pathway in the myogenic tone of posterior cerebral arteries.

AIMS: The goal of the current study was to determine whether the sphingosine kinase 1 (SK1)/sphingosine-1-phosphate (S1P) pathway is involved in myogenic vasoconstriction under normal physiological conditions. In the present study, we assessed whether endogenous S1P generated by pressure participates in myogenic vasoconstriction and which signaling pathways are involved in SK1/S1P-induced myogenic response under normal physiological conditions. METHODS AND RESULTS: We measured pressure-induced myogenic response, Ca(2+) concentration, and 20 kDa myosin light chain phosphorylation (MLC(20)) in rabbit posterior cerebral arteries (PCAs). SK1 was expressed and activated by elevated transmural pressure in rabbit PCAs. Translocation of SK1 by pressure elevation was blocked in the absence of external Ca(2+) and in the presence of mechanosensitive ion channel and voltage-sensitive Ca(2+) channel blockers. Pressure-induced myogenic tone was inhibited in rabbit PCAs treated with sphingosine kinase inhibitor (SKI), but was augmented by treatment with NaF, which is an inhibitor of sphingosine-1-phosphate phosphohydrolase. Exogenous S1P further augmented pressure-induced myogenic responses. Pressure induced an increase in Ca(2+) concentration leading to the development of myogenic tone, which was inhibited by SKI. Exogenous S1P further increased the pressure-induced increased Ca(2+) concentration and myogenic tone, but SKI had no effect. Pressure- and exogenous S1P-induced myogenic tone was inhibited by pre-treatment with the Rho kinase inhibitor and NADPH oxidase inhibitors. Pressure- and exogenous S1P-induced myogenic tone were inhibited by pre-treatment with S1P receptor blockers, W146 (S1P1), JTE013 (S1P2), and CAY10444 (S1P3). MLC(20) phosphorylation was increased when the transmural pressure was raised from 40 to 80 mmHg and exogenous S1P further increased MLC(20) phosphorylation. The pressure-induced increase of MLC(20) phosphorylation was inhibited by pre-treatment of arteries with SKI. CONCLUSIONS: Our results suggest that the SK1/S1P pathway may play an important role in pressure-induced myogenic responses in rabbit PCAs under normal physiological conditions.

Posterior reversible encephalopathy syndrome complicating intracranial hemorrhage after phenylpropanolamine exposure.

A 57-year-old woman suffered sudden onset of thunderclap headache after exposure to phenylpropanolamine (PPA), and subsequently developed posterior reversible encephalopathy syndrome (PRES) complicated by occipital intracranial hemorrhage (ICH) with cerebral vasoconstriction. PPA is well known to be associated with ICH and vasoconstriction, but this case illustrates the association with PRES. The danger of exposure to PPA and subsequent adverse events is quite low at present, but we must consider the possibility of exposure to medical agents in patients with repeated severe headache who have no organic disorder.

Metoprolol impairs resistance artery function in mice.

Acute ß-blockade with metoprolol has been associated with increased mortality by undefined mechanisms. Since metoprolol is a relatively high affinity blocker of ß(2)-adrenoreceptors, we hypothesized that some of the increased mortality associated with its use may be due to its abrogation of ß(2)-adrenoreceptor-mediated vasodilation of microvessels in different vascular beds. Cardiac output (CO; pressure volume loops), mean arterial pressure (MAP), relative cerebral blood flow (rCBF; laser Doppler), and microvascular brain tissue Po(2) (G2 oxyphor) were measured in anesthetized mice before and after acute treatment with metoprolol (3 mg/kg iv). The vasodilatory dose responses to ß-adrenergic agonists (isoproterenol and clenbuterol), and the myogenic response, were assessed in isolated mesenteric resistance arteries (MRAs; ∼200-µm diameter) and posterior cerebral arteries (PCAs ∼150-µm diameter). Data are presented as means ± SE with statistical significance applied at P < 0.05. Metoprolol treatment did not effect MAP but reduced heart rate and stroke volume, CO, rCBF, and brain microvascular Po(2), while concurrently increasing systemic vascular resistance (P < 0.05 for all). In isolated MRAs, metoprolol did not affect basal artery tone or the myogenic response, but it did cause a dose-dependent impairment of isoproterenol- and clenbuterol-induced vasodilation. In isolated PCAs, metoprolol (50 µM) impaired maximal vasodilation in response to isoproterenol. These data support the hypothesis that acute administration of metoprolol can reduce tissue oxygen delivery by impairing the vasodilatory response to ß(2)-adrenergic agonists. This mechanism may contribute to the observed increase in mortality associated with acute administration of metoprolol in perioperative patients.

The effect of propranolol on cerebrovascular reactivity to visual stimulation in migraine.

BACKGROUND: Propranolol is effective for migraine prophylaxis. However, its exact mechanism is not known. We postulated that the protective effect is due to the lowering of cerebrovascular reactivity (CVR). To verify this, we applied photic stimuli to migraineurs and analyzed the results. METHODS: We checked the mean flow velocity (MFV) of the posterior cerebral artery by transcranial Doppler in 22 migraineurs during a headache-free period and in 14 normal controls. During the photic stimulation, MFV was remeasured and the CVR was estimated in both groups. Migraineurs received prophylactic propranolol for 2 months, and they were then reevaluated for the above-mentioned parameters and assessed for a headache index (HI). RESULTS: There were no baseline differences in MFV between migraineurs and controls before treatment. Both groups showed a similar degree of increase in MFV with the photic stimulation, thus CVR was not significantly different between them. After the treatment period, CVR decreased significantly in migraineurs compared to baseline (p<0.01), although MFV remained unchanged. The prophylactic effect of propranolol treatment on symptomatic migraine was demonstrated on the HI, which significantly improved (p<0.05). CONCLUSIONS: Considering that CVR was decreased but the baseline MFV was not changed in the posterior cerebral artery prior to the visual stimulation in migraineurs after propranolol treatment, we assume that the protective effect of propranolol was not due to the direct effect on the cerebral vessels but due to the modulation of the CVR to sensory stimulation through its action on central centers associated with autonomic vascular tone.

Differences between cerebrovascular reactivity to L-arginine in the anterior and posterior cerebral circulation.

BACKGROUND: Cerebral endothelial function might be different in distinct cerebrovascular territory, thereby making these areas more susceptible to ischemia and stroke. Higher incidence and prevalence of stroke in males suggest that gender could have a strong influence on this difference. In order to evaluate cerebral endothelial function, we compared cerebrovascular reactivity (CVR) to L-arginine in the anterior and posterior cerebral circulation in healthy young males and females. METHODS: Thirty healthy subjects, 15 females (32.1 ± 7.1 years) and 15 males (32.2 ± 6.3 years), were included. The mean arterial velocity in the middle cerebral artery (MCA) and the posterior cerebral artery (PCA) was measured by transcranial Doppler sonography before and after intravenous infusion of L-arginine, and CVR to L-arginine was then calculated. RESULTS: CVR to L-arginine was significantly higher in PCA than in MCA in all subjects (19.2 ± 8.2 vs. 13.6 ± 7.1%, p ≤ 0.01). In addition, CVR to L-arginine was significantly more pronounced in females compared to males in PCA (22.7 ± 8.3 vs. 15.8 ± 6.7%, p ≤ 0.01) and MCA (16.8 ± 6.4 vs. 10.4 ± 6.4%, p < 0.05). CONCLUSIONS: Lower CVR to L-arginine and therefore lower cerebral endothelial function in the anterior cerebral circulation and in males might be related to the higher incidence of ischemia and stroke in the anterior cerebral circulation, particularly in males.

Cerebrovascular reactivity to l-arginine in the anterior and posterior cerebral circulation in migraine patients.

OBJECTIVE - Cerebral infarction preferentially affects the posterior cerebral artery distribution in migraine patients. The results obtained from the few known studies that have compared the anterior and posterior cerebral endothelial function are contradictory. To the best of our knowledge, cerebrovascular reactivity to L-arginine (CVR), measured by transcranial Doppler sonography (TCD), has not been previously used to determine the posterior cerebral endothelial function in migraine patients with (MwA) and without aura (MwoA). MATERIALS AND METHODS - Forty migraine patients without comorbidities (20 MwA, 20 MwoA) and 20 healthy subjects were included. By employing strict inclusion criteria, we avoided the possible vascular risk factors. Mean arterial velocity in the middle cerebral artery (MCA) and the posterior cerebral artery (PCA) was measured by TCD before and after infusion of L-arginine, and CVR to L-arginine was then calculated. RESULTS - All migraine patients had lower CVR to L-arginine in PCA (P = 0.002) and similar in MCA (P = 0.29) compared to healthy subjects. This difference was also present in MwA and MwoA compared to healthy subjects (P = 0.003). CONCLUSIONS - Lower CVR to L-arginine in PCA in migraine patients could associate migraine and cerebral infarcts that are more common in the posterior cerebral artery distribution.

Resistance artery adaptation to pregnancy counteracts the vasoconstricting influence of plasma from normal pregnant women.

Using a rat model, we investigated the effects of circulating factors in pregnancy on cerebrovascular and systemic vascular function by comparing myogenic reactivity, tone, and endothelial vasodilator production of the posterior cerebral artery (PCA) and mesenteric artery (MA) of nonpregnant (NP) animals perfused with nonpregnant and pregnant human plasma. Arteries from late pregnant (LP) animals were then perfused similarly to evaluate a potential adaptive effect of pregnancy on vessel function. A 3-hour exposure to pregnant plasma caused increased myogenic reactivity and tone in vessels from NP animals and produced a decreased endothelium-derived hyperpolarizing factor response in NP PCAs, findings that were not seen with MAs. The increased reactivity and tone noted in NP vessels was abolished when pregnant plasma was perfused through LP arteries, suggesting these vessels adapt during pregnancy to the vasoconstricting influence of pregnant plasma.

Role of Na+/Ca2+ exchanger-mediated Ca2+ entry in pressure-induced myogenic constriction in rat posterior cerebral arteries.

The involvement of Ca2+ entry via the Na+/Ca2+ exchanger (NCX) in myogenic constriction of rat posterior cerebral arteries was investigated. RT-PCR identified mRNA for NCX1, 2, and 3 in the arteries. Na+ removal increased [Ca2+]i, which was reduced by the NCX inhibitor SEA0400. SEA0400 inhibited the development, but not the steady-state, of pressure-induced myogenic constriction, whereas it decreased both the initial and sustained phases of [Ca2+]i elevation. These results suggest that Ca2+ entry via NCX is involved in the development, but not the steady-state, of pressure-induced myogenic constriction.

The influence of pregnancy and gender on perivascular innervation of rat posterior cerebral arteries.

The authors investigated the influence of pregnancy and gender on the density of trigeminal and sympathetic perivascular nerves in posterior cerebral arteries (PCA) and the reactivity to norepinephrine and calcitonin gene-related peptide (CGRP). PCAs were isolated from nonpregnant, late-pregnant, postpartum, and male rats, mounted and pressurized on an arteriograph chamber to obtain concentration-response curves to norepinephrine and CGRP. Arteries were immunostained for CGRP-, tyrosine hydroxylase-, and protein gene product 9.5 (PGP 9.5)-containing perivascular nerves, and nerve density was determined morphologically. Pregnancy had a trophic effect on trigeminal perivascular innervation (P < .01 vs male); however, this was not accompanied by a change in reactivity to CGRP. Sympathetic and PGP 9.5 nerve densities were not altered by pregnancy or gender, and there were no differences in reactivity to norepinephrine. Together, these results suggest that the increase in trigeminal innervation during pregnancy is more related to nociception than in controlling resting cerebral blood flow.