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J Cuevas

Publications and source records attributed to J Cuevas.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of calcitonin gene-related peptide on vascular resistance in rats: role of sex steroids.

It has been demonstrated in reflex-intact animals that the sensitivity to calcitonin gene-related peptide (CGRP) is increased during pregnancy and that this action is mediated by sex steroids but not by nitric oxide (NO). We assessed the effects of CGRP in the following groups of anesthetized ganglion-blocked rats: 1) pregnant, 2) ovariectomized, and 3) ovariectomized and treated with estradiol and progesterone. Changes in mean arterial pressure (MAP) were assessed after the administration of varying doses of CGRP. Decreases in MAP after CGRP administration were significantly greater in pregnant rats and ovariectomized rats administered sex steroids than in ovariectomized controls. The CGRP antagonist CGRP8-37 produced a pressor response of similar magnitude in both pregnant and ovariectomized rats. We also assessed the effects of CGRP and the modulating role of NO in the isolated uterine vascular bed preparation. CGRP reduced perfusion pressure to a greater degree in ovariectomized animals treated with sex steroids than in ovariectomized animals. This response was attenuated by pretreatment with an NO synthesis inhibitor. CGRP8-37 produced a similar increase in perfusion pressure in both groups. We conclude that 1) the increased vascular sensitivity observed during pregnancy or after treatment with sex steroids is in part mediated by NO, and 2) CGRP8-37 has a vasoconstrictor action of its own.

Animals↗
PubMed1998

Mammalian nicotinic receptors with alpha7 subunits that slowly desensitize and rapidly recover from alpha-bungarotoxin blockade.

One of the most abundant nicotinic receptors in the nervous system is a species that contains the alpha7 gene product, rapidly desensitizes, and binds alpha-bungarotoxin with great affinity. The receptor has a high relative permeability to calcium and performs a variety of functions including presynaptic modulation of transmitter release and postsynaptic generation of synaptic currents. Fast excitatory transmission in mammalian intracardiac ganglia is mediated primarily by nicotinic receptors, and although intracardiac ganglion neurons express the alpha7 gene, no toxin-sensitive response has been detected previously in them. We report here that whole-cell patch-clamp recordings from freshly dissociated intracardiac ganglion neurons reveal a nicotinic response that desensitizes slowly and is blocked by alpha-bungarotoxin in a rapidly reversible manner. The only rat gene previously thought capable of forming such receptors was alpha9, but no evidence suggests that the alpha9 gene is expressed in neurons. We find that reverse transcription (RT)-PCR detects alpha7 but not alpha9 mRNA in the ganglia. In addition, the pharmacology of the nicotinic response is typical of alpha7-containing receptors but differs in several respects from that expected for alpha9. Binding experiments with immunotethered receptors identifies a ganglionic species that contains the alpha7 gene product. Moreover, intracellular perfusion of the cells with an anti-alpha7 monoclonal antibody specifically reduces the amplitude of the toxin-sensitive response. The results indicate that alpha7-containing receptors are responsible for the slowly desensitizing, toxin-reversible response and suggest that the receptors are modified in cell-specific ways to influence their functional properties.

Acetylcholine↗
PubMed1998

alpha-conotoxin EpI, a novel sulfated peptide from Conus episcopatus that selectively targets neuronal nicotinic acetylcholine receptors.

We have isolated and characterized alpha-conotoxin EpI, a novel sulfated peptide from the venom of the molluscivorous snail, Conus episcopatus. The peptide was classified as an alpha-conotoxin based on sequence, disulfide connectivity, and pharmacological target. EpI has homology to sequences of previously described alpha-conotoxins, particularly PnIA, PnIB, and ImI. However, EpI differs from previously reported conotoxins in that it has a sulfotyrosine residue, identified by amino acid analysis and mass spectrometry. Native EpI was shown to coelute with synthetic EpI. The peptide sequence is consistent with most, but not all, recognized criteria for predicting tyrosine sulfation sites in proteins and peptides. The activities of synthetic EpI and its unsulfated analogue [Tyr15]EpI were similar. Both peptides caused competitive inhibition of nicotine action on bovine adrenal chromaffin cells (neuronal nicotinic ACh receptors) but had no effect on the rat phrenic nerve-diaphragm (muscle nicotinic ACh receptors). Both EpI and [Tyr15]EpI partly inhibited acetylcholine-evoked currents in isolated parasympathetic neurons of rat intracardiac ganglia. These results indicate that EpI and [Tyr15]EpI selectively inhibit alpha3beta2 and alpha3 beta4 nicotinic acetylcholine receptors.

Amino Acid Sequence↗
PubMed1997

Heterogeneity of nicotinic receptor class and subunit mRNA expression among individual parasympathetic neurons from rat intracardiac ganglia.

Neurons have the potential to form thousands of distinct neuronal nicotinic receptors from the eight alpha and three beta subunits that currently are known. In an effort to determine how much of this potential complexity is realized among individual neurons, we examined the nicotinic pharmacological and biophysical properties and receptor subunit mRNA expression patterns in individual neurons cultured from rat epicardial ganglia. Analysis of the whole-cell pharmacology of these neurons showed a diversity of responses to the agonists acetylcholine, nicotine, cytisine, and 1,1-dimethyl-4-phenylpiperazinium, suggesting that a heterogeneous population of nicotinic receptor classes, or subtypes, is expressed by individual neurons. Single-channel analysis demonstrated three distinct conductances (18, 24, and 31 pS), with patches from different neurons containing different combinations of these channel classes. We used single-cell RT-PCR to examine nicotinic acetylcholine receptor (nAChR) subunit mRNA expression by individual neurons. Although mRNAs encoding all eight neuronal nAChR subunits for which we probed (alpha 2-alpha 5, alpha 7, beta 2-beta 4) were present in multicellular cultures, we found that individual epicardial neurons express distinct subsets of these nAChR subunit mRNAs. These results suggest that individual epicardial neurons express distinct arrays of nAChR subunits and that these subunits may assemble into functional receptors with distinct and variable subunit composition. This variable receptor subunit expression provides an explanation for the diversity of pharmacological and single-channel responses we have observed in individual neurons.

Action Potentials↗
PubMed1997

Passive and active membrane properties of isolated rat intracardiac neurons: regulation by H- and M-currents.

The electrical characteristics of isolated neonatal rat intracardiac neurons were examined at 22 and 37 degrees C using the perforated-patch whole cell recording technique. The mean resting membrane potential was -52.0 mV at 37 degrees C and exhibited no temperature dependence. Lowering the temperature from 37 to 22 degrees C decreased the mean input resistance from 854 to 345 Momega, respectively, and reduced the membrane time constant approximately threefold yielding a Q10 of 2.1. Hyperpolarizing current pulses induced time-dependent rectification of the voltage response in all neurons at both temperatures. This behavior was previously not observed in dialyzed neurons and was reversibly blocked by external Cs+ (2 mM) but not Ba2+ (1 mM). Voltage-clamp studies of isolated neurons revealed a hyperpolarization-activated inward current. This inwardly rectifying conductance was isolated from other membrane currents using external Cs+. The time and voltage dependence of this current is consistent with Ih and contributes to the passive electrical properties of rat intracardiac neurons. In >90% of the neurons studied, depolarizing currents evoked firing of multiple, adapting, action potentials at 22 degrees C. The number of action potentials increased with current strength producing a mean discharge of 5.1 (+100 pA, 1 s pulse), which was attenuated at 37 degrees C to a mean of 1.4. The amplitude and kinetics of the slow, muscarine-sensitive inward and outward currents (IM) were highly temperature dependent. Lowering the temperature from 37 to 22 degrees C reduced the steady-state current amplitude by approximately one-third and the rate of deactivation of IM by six- to ninefold at all voltages examined. The average Q10 for the time constant of deactivation of IM was 3.7 +/- 0.3 (mean +/- SE). Acetylcholine (ACh) induced tonic discharges in response to depolarizing currents (+100 pA, 1 s pulse) at both temperatures. This effect of ACh was inhibited by the muscarinic receptor antagonists, pirenzepine (100 nM), and mL-toxin (60 nM). At 37 degrees C, a mean discharge of 1.5 was increased to 23.5 in the presence of ACh. A similar switch from phasic to tonic discharge was also produced by the potassium channel inhibitors, Ba2+ (1 mM) and uridine-5'-triphosphate (UTP; 100 microM), whereas cadmium, 4-aminopyridine, apamin, charybdotoxin, and dendrotoxin did not alter discharge activity. The pharmacological sensitivity profile and temperature dependence of the active membrane properties are consistent with the muscarine-sensitive potassium current (IM) regulating the discharge activity in rat intracardiac neurons.

Acetylcholine↗
PubMed1997

M4 muscarinic receptor activation modulates calcium channel currents in rat intracardiac neurons.

Modulation of high-voltage-activated Ca2+ channels by muscarinic receptor agonists was investigated in isolated parasympathetic neurons of neonatal rat intracardiac ganglia using the amphotericin B perforated-patch whole cell recording configuration of the patch-clamp technique. Focal application of the muscarinic agonists acetylcholine (ACh), muscarine, and oxotremorine-M to the voltage-clamped soma membrane reversibly depressed peak Ca2+ channel current amplitude. The dose-response relationship obtained for ACh-induced inhibition of Ba2+ current (IBa) exhibited a half-maximal inhibition at 6 nM. Maximal inhibition of IBa amplitude obtained with 100 microM ACh was approximately 75% compared with control at +10 mV. Muscarinic agonist-induced attenuation of Ca2+ channel currents was inhibited by the muscarinic receptor antagonists pirenzepine (</=300 nM) and m4-toxin (</=100 nM), but not by AF-DX 116 (300 nM) or m1-toxin (60 nM). The dose-response relationship obtained for antagonism of muscarine-induced inhibition of IBa by m4-toxin gave an IC50 of 11 nM. These results suggest that muscarinic agonist-induced inhibition of high-voltage-activated Ca2+ channels in rat intracardiac neurons is mediated by the M4 muscarinic receptor. M4 receptor activation shifted the voltage dependence and depressed maximal activation of Ca2+ channels but had no effect on the steady-state inactivation of Ca2+ channels. Peak Ca2+ channel tail current amplitude was reduced >/=30% at +90 mV in the presence of ACh, indicating a voltage-independent component to the muscarinic receptor-mediated inhibition. Both dihydropyridine- and omega-conotoxin GVIA-sensitive and -insensitive Ca2+ channels were inhibited by ACh, suggesting that the M4 muscarinic receptor is coupled to multiple Ca2+ channel subtypes in these neurons. Inhibition of IBa amplitude by muscarinic agonists was also observed after cell dialysis using the conventional whole cell recording configuration. However, internal perfusion of the cell with 100 microM guanosine 5'-O-(2-thiodiphosphate) trilithium salt (GDP-beta-S) or incubation of the neurons in Pertussis toxin (PTX) abolished the modulation of IBa by muscarinic receptor agonists, suggesting the involvement of a PTX-sensitive G-protein in the signal transduction pathway. Given that ACh is the principal neurotransmitter mediating vagal innervation of the heart, the presence of this inhibitory mechanism in postganglionic intracardiac neurons suggests that it may serve for negative feedback regulation.

Acetylcholine↗
PubMed1996

Vasoactive intestinal polypeptide modulation of nicotinic ACh receptor channels in rat intracardiac neurones.

1. The effects of vasoactive intestinal polypeptide (VIP) on isolated parasympathetic neurones of rat intracardiac ganglia were examined under voltage clamp using dialysed and perforated patch whole-cell and excised outside-out membrane patch recording configurations. 2. VIP reversibly potentiated nicotinic ACh-evoked whole-cell currents, with half-maximal potentiation (EC50) obtained with 260 pM VIP. However, VIP had no effect on muscarinic ACh-evoked currents, ATP-evoked currents, or depolarization-activated ionic currents in these neurones. 3. VIP-induced potentiation of nicotinic ACh-evoked whole-cell currents was observed following cell dialysis, and was inhibited reversibly by bath application of the VIP receptor-binding inhibitor L-8-K (5 microM) or the neuronal nicotinic receptor antagonist mecamylamine (3 microM). 4. The signal transduction pathway mediating VIP-induced potentiation of nicotinic ACh-evoked currents involves a guanine nucleotide-binding protein (G-protein) but not cyclic AMP. Intracellular application of 100 microM GDP-beta-S, or pre-incubation of neurones with pertussis toxin, inhibited VIP-induced potentiation of ACh-evoked whole-cell currents. 5. In outside-out membrane patches, co-application of ACh (4 microM) and VIP (4 nM) decreased the duration of closings between bursts and clusters of bursts of ACh single-channel activity relative to control (4 microM, ACh alone). VIP, however, did not alter single ACh receptor channel current amplitude, duration of closings and openings within a burst, or mean burst duration. 6. VIP-induced modification of nicotinic ACh receptor channel kinetics results in an increase in the open-channel probability which is sufficient to account for the VIP-mediated potentiation of nicotinic ACh-evoked whole-cell currents. 7. The potentiation of nicotinic ACh-evoked currents by VIP is likely to account for the altered neuronal activity observed in the mammalian intracardiac ganglia in vivo and consequent changes in heart rate and cardiac contractility.

Acetylcholine↗
PubMed1996

A new case of fibrochondrogenesis from Spain.

A rare, neonatally lethal chondrodysplasia with histological characteristics was first described in 1978 and the authors named the condition fibrochondrogenesis. Here we report the eighth published case of fibrochondrogenesis. This was identified in a population of 1,158,067 consecutive livebirths, so we can assume that this figure should be the minimal prevalence for livebirths.

Abnormalities, Multiple↗
PubMed1995

The role of nitric oxide in the altered vascular reactivity of pregnancy in the rat.

1. Pregnancy is characterized by a decrease in systemic vascular resistance and a blunting of the angiotensin II (AII) pressor response. We studied the role of nitric oxide (NO) and prostanoids in these vascular changes of pregnancy in anaesthesized, ganglion blocked non-pregnant and pregnant rats. 2. Inhibition of NO synthesis with NG-nitro-L-arginine methyl ester (L-NAME) led to an increase in mean arterial pressure (MAP) which was of a significantly greater magnitude in pregnant rats in late gestation than in non-pregnant rats, or rats in mid-gestation. 3. The pressor response to varying doses of AII was attenuated during late pregnancy, and this attenuation was partially reversed by L-NAME. 4. The pressor response to varying doses of a vasoconstrictor, phenylephrine (PE), was also attenuated in late pregnancy. However, this attenuation was not reversed by L-NAME. 5. Inhibition of prostanoid biosynthesis with meclofenamate did not alter basal MAP, nor the pressor response to varying doses of AII or PE in pregnant and non-pregnant animals. 6. It is concluded that (a) increased NO synthesis occurs during late gestation and contributes both to the decrease in systemic vascular resistance, as well as the blunting of the pressor response to AII during pregnancy, and (b) prostaglandins are not important in the maintenance of basal vascular tone, or the blunting of the pressor response to AII during pregnancy.

Angiotensin II↗
PubMed1994

Local anaesthetic blockade of neuronal nicotinic ACh receptor-channels in rat parasympathetic ganglion cells.

1 The effects of the local anaesthetics QX-222 and procaine on nicotinic acetylcholine (ACh)-evoked currents in cultured parasympathetic cardiac neurones of the rat were investigated by use of the whole-cell, perforated-patch, and outside-out recording configurations of the patch clamp method. 2 QX-222 and procaine, applied to the extracellular surface, reversibly inhibited the peak amplitude of the whole-cell nicotinic ACh-evoked current in a concentration-dependent manner, with half-maximal inhibitory concentrations (IC50) of 28 microM and 2.8 microM, respectively, at -80 mV. In these neurones, the sustained inward current mediated by M1 muscarinic receptor activation was unaltered by QX-222, and neither local anaesthetic affected the adenosine 5'-triphosphate (ATP)-evoked current. 3 QX-222 and procaine block of nicotinic ACh-evoked inward current was voltage-dependent and enhanced by hyperpolarization. An e-fold change in their dissociation equilibrium constants (Kd) resulted from a 62 mV and a 122 mV change in membrane potential, respectively. 4 Both local anaesthetics produce a concentration-dependent increase in the half-time of decay of the nicotinic ACh-evoked inward current. 5 Measurements of unitary currents in outside-out patches showed that QX-222 reversibly increased the mean burst duration and closed time and reduced the mean channel open time and open-state probability of the nicotinic ACh receptor-channel (AChR) in a concentration-dependent manner. 6 The Kd and voltage sensitivity of local anaesthetic block of the nicotinic AChR in rat intracardiac neurones suggests that the pore-forming region of this channel differs from that of the AChR in frog and rat skeletal muscle and from the neuronal alpha 4 beta 2 ACh receptor-channel.

Acetylcholine↗
PubMed1993

Papular xanthoma in children: report and immunohistochemical study.

Papular xanthoma was diagnosed in a 14-month-old boy. The eruption cleared spontaneously within four years. Immunohistopathologic study revealed that the predominant foamy histiocytic cells had the phenotypic features of the dermal dendrocyte. Giant multinucleated cells, which showed characteristics of monocyte-derived macrophages, were also present. We suggest classifying diseases derived from dermal dendrocytes into a separate group of histiocytoses.

Giant Cells↗
PubMed1993

NO is more important than PGI2 in maintaining low vascular tone in feto-placental vessels.

The endothelial cells of the human umbilical artery and vein release the vasodilators prostacyclin [prostaglandin (PG) I2] and nitric oxide (NO). However, the role of these two substances in the maintenance of vasodilator tone in the feto-placental circulation is not known. Studies were therefore undertaken to compare the relative release of PGI2 and NO from perfused segments (10 cm) of endothelium-intact human umbilical artery (HUA) and vein (HUV) utilizing the cascade bioassay. The endothelium-denuded bovine pulmonary arterial strip was used as the detector tissue because this tissue relaxes equally to various concentrations of PGI2 and S-nitroso-N-acetylpenicillimine (SNAP), which acts by releasing NO. The basal release of NO from the HUA was approximately five times greater than that of PGI2. After stimulation with A-23187, the release of NO from HUV was five to six times greater, and from the HUA, the release was three times greater compared with the PGI2. SNAP was significantly more potent compared with PGI2 in relaxing endothelium-denuded rings of human umbilical and chorionic plate arteries in vitro. These studies suggest that NO is more important than PGI2 for maintenance of low vascular tone in feto-placental vessels, because there is a greater release of NO from the HUA and HUV, and NO is more potent in relaxing endothelium-denuded feto-placental vessels in vitro relative to PGI2.

Animals↗
PubMed1992

Hypoxia inhibits calcium influx in rabbit basilar and carotid arteries.

We examined the hypothesis that hypoxia inhibits Ca2+ influx in isolated rabbit common carotid, internal carotid, and basilar arteries. In arteries mounted for measurement of isometric tension and exposed to 122 mM K+ in Ca(2+)-free Krebs, cumulative addition of Ca2+ produced Ca(2+)-force relations that were right-shifted by hypoxia (PO2 approximately 15 Torr) with no decrease in maximum force attained. In arteries precontracted with 122 mM K+, exposure to hypoxia produced relaxations whose rates and magnitudes were enhanced by reductions in bath Ca2+ from 8.0 to 0.8 mM. Using an ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid method for 3-min 45Ca influx measurements, modified for use in rabbit basilar and carotid arteries, we found that resting levels of Ca2+ influx (mumol.min-1.kg dry wt-1) were significantly higher in basilar (67 +/- 1, n = 10) than in internal carotid (27 +/- 1, n = 12) or common carotid (33 +/- 1, n = 12) arteries. K+ stimulation increased Ca2+ influx more than two-fold compared with control in all three artery types, and hypoxia inhibited this increase by 74% in basilar, 49% in internal carotid, and 33% in common carotid arteries. Exposure to 10 microM serotonin and 100 microM uridine 5'-triphosphate (UTP) also increased Ca2+ influx, but these increases were less than observed during K+ contractions and averaged 10 (basilar), 31 (internal carotid), and 82% (common carotid) above control. Hypoxia completely inhibited serotonin- and/or UTP-induced increases in Ca2+ influx in basilar and internal carotid segments and inhibited 47% of this increase in the common carotid segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of H+ on ATP-regulated K+ channels in feline ventricular myocytes.

Using patch-clamp techniques, we examined the effects of pH on properties of ATP-regulated K+ channels in single myocytes isolated from cat left ventricles. ATP-K+ channels of inside-out patches were bilaterally exposed to 140 mM K+ solutions (22 degrees C). In the absence of ATP and Mg2+, the channels had a linear current-voltage relationship during hyperpolarizing pulses (20-100 mV negative to the reversal potential) at both intracellular pH (pHi) 7.4 and 6.5, but the slope conductance was 66 +/- 2 pS at pHi 7.4 and 46 +/- 2 pS at pHi 6.5. Lowering pHi from 7.4 to 6.5 increased the mean open time (from 15.9 +/- 4.6 to 35.9 +/- 7.9 ms, P less than 0.01) but decreased the open-state probability measured at 50 mV positive to the reversal potential (from 0.35 +/- 0.04 to 0.16 +/- 0.04, P less than 0.01). However, in the presence of both 0.2 mM ATP and 1 mM MgCl2, lowering pHi from 7.4 to 6.5 increased the mean open time (from 5.0 +/- 2.6 to 17.9 +/- 5.9 ms, P less than 0.01) and the open-state probability (from 0.025 +/- 0.010 to 0.098 +/- 0.024, P less than 0.01). These data indicate that increases in intracellular H+ concentration modulate cardiac ATP-K+ channel properties. Ischemia-associated decreases in pHi may enhance the opening of cardiac ATP-regulated K+ channels and resultant action potential shortening.

Adenosine Triphosphate↗
PubMed1990

Electrophysiological properties and responses to simulated ischemia in cat ventricular myocytes of endocardial and epicardial origin.

In multicellular preparations, there are differences in action potential configuration between endocardium and epicardium, and electrophysiological alterations induced by ischemia are more drastic in epicardium than in endocardium. The present study was designed to examine electrophysiological properties of single cardiac myocytes enzymatically isolated from the endocardial and epicardial surfaces of the cat left ventricle and to determine whether the differential responses to ischemia of intact tissue occur in single cells. Action potentials recorded from the isolated single cells of epicardial surface had lower action potential amplitude and a prominent notch between phase 1 and phase 2, compared with those of the cells isolated from the endocardial surface; these findings are similar to those in intact endocardial and epicardial preparations. Resting membrane potentials recorded from both endocardial and epicardial single cells were sensitive to the change in extracellular K+ concentration and had properties of a K+ electrode. Action potential duration was frequency dependent in both cell types and was shorter in epicardial cells than in endocardial cells at a stimulation rate of 3 Hz. When the cells were superfused with Tyrode's solution that was altered to mimic an ischemic environment in vivo (PO2, 30-40 mm Hg; pH 6.8; [K+], 10 mM; and glucose free), resting membrane potential, action potential amplitude, and action potential duration were reduced, and the refractory period was shortened in both endocardial and epicardial single cells, but there were no differences in the degree of changes in action potentials and refractory periods induced between the two cell types. Action potential changes induced by L-alpha-lysophosphatidylcholine (5-40 mg/l) were also similar in endocardial and epicardial single cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1989

Direct effects of graded hypoxia on intact and denuded rabbit cranial arteries.

In isolated rabbit common carotid, internal carotid, and basilar arteries denuded of endothelium, mounted for measurement of contractile activity, and contracted with 10 microM serotonin (common and internal carotid) or 100 microM uridine 5'-triphosphate (UTP; basilar), 20 min of severe (PO2 = 15 Torr) and moderate (PO2 = 35 Torr) hypoxia relaxed initial tensions to 17, 6, and 16% and 18, 7, and 61% of control, respectively. The corresponding values in arteries contracted with 120 mM potassium-Krebs solution were 42, 60, and 73% and 57, 72, and 88%. These data indicate that the main determinants of the responses to hypoxia were intrinsic to the vessel walls of these arteries and that complete depolarization attenuated but did not eliminate the effects of these mechanisms. Superimposed on these intrinsic mechanisms were the effects of the endothelium, which were evaluated by several methods, including integration of the area between the 20-min response time courses of corresponding intact and denuded segments. Positive and negative integrated area values indicated endothelial vasoconstrictor [endothelium-derived contracting factor (EDCF)] and vasodilator [endothelium-derived relaxing factor (EDRF)] influences, respectively. In common carotid, internal carotid, and basilar segments contracted with serotonin and/or UTP, these areas averaged 770, 354, and 44 min% during severe and 491, 189, and -411 min% during moderate hypoxia. Corresponding values during potassium contraction were 217, -271, and -356 min% and 52, -177, and -54 min%. Together, these findings suggest that 1) intrinsic vascular mechanisms contribute significantly to hypoxic cerebral vasodilation in the rabbit, 2) EDCF is more prominent but also may be more sensitive to depolarization than EDRF, 3) hypoxia promotes the simultaneous release of both EDCF and EDRF, and 4) the ratio of EDCF to EDRF released during hypoxia decreases as one moves from the rabbit common carotid to the internal carotid to the basilar arteries.

Animals↗