PubMed Health⌕ Search

Biomedical subjects

W J Pearce

Publications and source records attributed to W J Pearce.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1992

Pregnancy-induced changes in ovine cerebral arteries.

We examined the effects of pregnancy on the ovine cerebral vasculature by comparing several characteristics of isolated endothelium-intact segments of three intracranial arteries including the middle cerebral (MCA), posterior communicating (PC), and basilar (BAS) arteries taken from pregnant sheep (138-143 days gestation, term approximately 145 days) and nonpregnant controls. For comparison, segments of the extracranial common carotid (COM) artery were also studied. With pregnancy, vessel water content increased (5.4-5.8%) in all arteries except the PC. Additionally, cellular protein content increased in all arteries (4.4-50.0%). Arterial stiffness, as determined by passive stress-strain determinations, was significantly decreased during pregnancy in the MCA but not in the larger arteries. Maximum contractile responses, when normalized to vessel wall cross-sectional area, were consistently greater in arteries from pregnant than in those from nonpregnant animals (10.1-49.7%). Relaxation to the endothelium-independent guanylate cyclase stimulator S-nitroso-N-acetyl penicillamine (SNAP) increased with pregnancy only in the distal MCA (approximately 17%). Endothelium-dependent relaxation to the calcium ionophore A23187 decreased only in the larger and more proximal COM (-39%). Thus pregnancy was associated with an increase in production of contractile force, a decrease in peripheral vascular stiffness, a decrease in the relaxant response to A23187 in the COM, and an increase in the relaxant response to SNAP in the MCA. Together, these findings indicate that pregnancy has widespread and important vessel specific cerebrovascular consequences that affect not only arterial composition, but also contractility and endothelial reactivity.

Analysis of Variance↗
PubMed1991

Developmental changes in ovine cerebral artery composition and reactivity.

We have examined age-related changes in segments of common carotid (Com), basilar (Bas), posterior communicating (PC), and middle cerebral (MC) arteries taken from 14 near-term fetal lambs, 62 newborn lambs 3-7 days old, and 42 adult nonpregnant sheep. Transition from fetal to newborn life was associated with a decreased water content in all arteries ranging from 0.6% (Com) to 2.3% (Bas), no change in the relative content of cellular protein, an increase in wall thickness ranging from 4% (MC) to 26% (Com), an increase in maximum contractile tension ranging from 18% (MC) to 82% (Com), an increase in stiffness, an increase in the maximum active stress ranging from 6% (Bas) to 43% (Com), a decrease in the amine-to-potassium ratio (calculated as the maximum response to 10 microM serotonin with 20 microM histamine divided by the maximum response to 122 mM K+) ranging from 8% (Bas) to 51% (Com), and a decrease in the norepinephrine-to-potassium ratio ranging from 2.1% (Bas) to 56% (Com). Thus developmental changes associated with the transition from fetal to newborn life were much more pronounced in the larger, more proximal Com than in the smaller, more distal cerebral arteries, suggesting that, at term, the cerebral arteries are more mature both functionally and structurally than the Com arteries. Similarly, the transition from newborn to adult life was associated with much greater changes in Com characteristics than with those of the cerebral arteries. These studies demonstrate that the effects of aging vary considerably along the cerebrovascular tree and that conclusions based on developmental studies of large systemic arteries cannot be freely extrapolated to the smaller arteries of the circle of Willis.

Aging↗
PubMed1991

Dietary lipids modify receptor- and non-receptor-dependent components of alpha 1-adrenoceptor-mediated contraction.

Dietary lipid modulation of alpha-adrenoceptor (adrenergic receptor)- and non-adrenoceptor-mediated contractile properties of isolated rat abdominal aortic segments were assessed during the early developmental period. Rats were raised from conception to 90 days of age on semisynthetic diets containing various types and amounts of lipids. Aortic segments from three groups of rats fed high-fat diets (15% wt/wt) consisting of olive oil, corn oil, or lard as the sole lipid sources were compared with those from rats fed a low-fat control diet containing corn oil (5% wt/wt). alpha-Adrenoceptor activities were assessed by measuring the norepinephrine dose response of the tissue rings with and without partial inactivation of alpha-receptors by benextramine. alpha-Adrenoceptor sensitivity to norepinephrine increased, whereas receptor affinity decreased significantly in rats raised on high-fat diets. Qualitative features of dietary lipids influenced non-adrenoceptor-dependent aspects of vascular contractility. Diets rich in polyunsaturated fatty acids (high- and low-fat corn oil) raised the maximum response to norepinephrine and the contractile response to 60 mM potassium compared with more-saturated diets (olive oil and lard). These results demonstrate an effect of chronic feeding of high dietary fat on alpha-adrenoceptor-mediated contractility of abdominal aortic rings from young Sprague-Dawley rats. Qualitative features of dietary lipids also appear to modify receptor-independent parameters of the contractile response of the arterial tissue rings in these animals.

Animals↗
PubMed1991

Developmental aspects of endothelial function.

We believe that the mechanisms through which nitric oxide and guanylate cyclase produce relaxation are fully functional in cerebral arteries at term in the fetal sheep and probably also in the term human infant. The relation between cGMP levels and the degree of relaxation varies both with age and with the relaxant used in a vessel specific manner. The factors underlying this variability constitute a fruitful area for future research and include possible age-related changes in membrane potential, calcium channel density and currents, and the participation of cGMP-independent mechanisms, to name only a few. Between fetal and newborn life, the biotransformation of nitroglycerin appears to improve significantly, particularly in the smaller more distal cerebral arteries. This improvement may be a clue to other important vascular metabolic and enzymatic changes that occur during the perinatal period. At the endothelial level, responses to A23187, an index of maximum endothelial vasodilator capacity, are relatively stable across the perinatal period and do not change consistently with age across all arteries. More importantly, large arteries, such as the common carotid, appear to relax better than the smaller cerebral arteries, and this difference is greater in fetal than in adult arteries. Responses to ADP disappear with age in the common carotid, but remain or even become enhanced in the cerebral arteries, thus illustrating the key role played by changes in receptor type and distribution in development and maturation.

Adenosine Diphosphate↗
PubMed1990

Effects of methylene blue on hypoxic cerebral vasodilatation in the rabbit.

The present studies were conducted to examine the role of cerebrovascular guanylate cyclase in hypoxic cerebral vasodilatation. In arteries mounted in vitro for measurements of isometric tension, 20 min of hypoxia (bath oxygen partial pressure, approximately 15 Torr) significantly increased cyclic GMP levels from 16 to 32, from 15 to 25 and from 20 to 38 pmol/g in rabbit common carotid, internal carotid and basilar arteries. These increases were blocked either by pretreatment with 3 microM methylene blue, or by removal of the vascular endothelium. Methylene blue also significantly delayed hypoxic relaxation in the basilar and internal carotid arteries, and blocked transient hypoxic vasoconstriction in the common carotid. Together, these in vitro results demonstrate that vascular cytosolic guanylate cyclase participates in an endothelium-dependent manner in the direct effects of hypoxia on cerebral arteries, and that the nature of this participation varies significantly between arteries. When methylene blue (20 mg/kg) was administered in vivo, however, it had no effect on the magnitude of hypoxic cerebral vasodilatation as determined by both local (mass spectrometry) and global (venous outflow) methods of blood flow measurement. This latter finding suggests that: 1) large and small cerebral arteries may differ significantly in terms of either endothelial function or sensitivity to methylene blue; or 2) feedback regulation of other mechanisms of hypoxic cerebral vasodilatation compensate for the effects of guanylate cyclase inhibition. Additional experiments using other inhibitors of cytosolic guanylate cyclase and/or vessels isolated from the cerebral microcirculation will be necessary to distinguish between these possibilities.

Animals↗
PubMed1990

Effects of hypoxia on contractility of isolated fetal lamb cerebral arteries.

We studied the contractile properties of isolated cerebral arteries in near term fetal lambs, as well as the magnitudes and rates of relaxation during moderate hypoxia. Paired 5-mm segments of basilar, middle cerebral, posterior communicating, and common carotid arteries were suspended in a temperature controlled bath and isometric tension measured during 122 mM K(+)-induced contractions. In one vessel of each pair hypoxia was imposed by switching the bubbling gas from 95% O2 + 5% CO2 to 95% N2 + 5% CO2 4 minutes into a K+ contraction, thus lowering the bath PO2 to approximately 15 Torr. After 15 min exposure to hypoxia the middle cerebral artery had relaxed 61%, the posterior communicating 46%, the basilar 44%, and the common carotid only 18% compared to normoxic controls. All cerebral arteries relaxed relatively rapidly (relaxation rates of 42-45 x 10(-4) s-1), whereas the common carotid relaxed slowly (20 x 10(-4) sec-1). The data indicate that these cerebral arteries play an important role in regulating blood flow responses during hypoxemia in intact fetuses.

Animals↗
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↗
PubMed1987

Developmental changes in thickness, contractility, and hypoxic sensitivity of newborn lamb cerebral arteries.

The present studies were conducted to examine the possibility that the increased vulnerability of the newborn brain to hypoxia may be due to age-related differences in vascular thickness and contractility. Segments of rostral choroidal (RC), posterior communicating (PC), basilar (B), and common carotid (CC) arteries were taken from 3- to 7-day-old lambs (n = 11) and adult sheep (n = 8) and studied using standard in vitro techniques. In lamb cerebral arteries, maturation was associated with significant increases in vessel thickness and tension generation. Because the increases in tension generation (77, 90, and 135% in PC, B, and RC segments) were proportionately greater than the corresponding increases in thickness (45, 75, and 34% in PC, B, and RC), force per unit area increased with maturation in the cerebral arteries. In the CC segments, the age-related increases in thickness (117%) were greater than the increases in tension generation (30%), such that average force per unit area was actually greater in the lamb than in the sheep. In response to hypoxia (PO2 less than 15 torr), all vessels exhibited significant relaxation relative to normoxic controls, although the rates and magnitudes of relaxation varied considerably. In the sheep, the carotid exhibited rapid relaxation of small magnitude (21%), whereas the cerebral arteries relaxed more slowly and more completely (56, 52, and 45% in PC, B, and RC). In contrast, the lamb carotid segments relaxed more slowly than the cerebral arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Diltiazem and autoregulation of canine cerebral blood flow.

Recent in vitro evidence suggests the existence of stretch-activated calcium channels in cerebrovascular smooth muscle. These channels, which may play a role in cerebral autoregulation, also appear resistant to antagonism by the benzothiazepine calcium antagonist diltiazem, an agent known to block potential-sensitive and receptor-operated calcium channels. If cerebral autoregulation involves stretch-sensitive diltiazem-resistant calcium channels, then autoregulation should remain intact during vasodilatation produced by diltiazem. The present study was conducted to test this hypothesis. Using a canine cerebral venous outflow preparation, experiments were first performed to determine the optimum dose and route of administration for diltiazem. Although continuous i.v. diltiazem (1-100 micrograms/kg/min) did not increase cerebral perfusion at any normotensive dose, i.a. (lingual artery) diltiazem at 10.0 micrograms/kg/min increased cerebral blood flow by 36% and decreased cerebrovascular resistance by 31% without significant effects on blood gas levels, cerebral oxygen uptake, cardiac output or mean arterial pressure. In autoregulation experiments, 10.0 micrograms/kg/min of diltiazem significantly attenuated but did not eliminate autoregulatory responses to increases (inflation of an aortic balloon) and decreases (hemorrhage) in cerebral perfusion pressure. Autoregulatory responses to increases and decreases in perfusion pressure were equally affected by diltiazem, but both were unaffected by i.a. saline. These data support the view that cerebral autoregulation involves both diltiazem-sensitive and diltiazem-resistant mechanisms. The diltiazem-resistant mechanisms, which may include the proposed population of stretch-sensitive calcium channels appear to account for up to one-half of the autoregulatory capacity in the cerebral circulation.

Animals↗
PubMed1986

The use of Gore-Tex E-PTFE bonded to silicone rubber as an alloplastic implant material.

The purpose of this paper is to evaluate the use of an alloplastic material, Gore-Tex Soft Tissue Patch, which when bonded to silicone rubber (Silastic) may represent a more "ideal" implant material. It's use in the rabbit model is compared to Silastic alone, Supramid Mesh, and cartilage control. Grafts were harvested at 3 weeks and 3 months, and the histologic findings were reviewed. Our results demonstrate that the implant is quite inert (minimal tissue reaction), allows for tissue ingrowth with reduced capsule formation, and protects the silicone rubber infrastructure from encapsulation. These findings suggest that Gore-Tex Soft Tissue Patch bonded to silicone rubber is a superior implant material and is worthy of consideration for clinical applications.

Animals↗