Biomedical subjects

S H Nelson

Publications and source records attributed to S H Nelson.

At least 19 recordsLinked to original sources

PubMed2001

Effects of hemoglobin-based blood substitutes on vasoactivity of rat aortic rings.

Our objective is to characterize the vasoactive properties of a 10% alphaalpha diaspirin cross-linked human hemoglobin (alphaalphaHb) and to test the hypothesis that sodium nitroprusside (SNP)-induced relaxation is inhibited in the presence of alphaalphaHb. Experiments were performed on aortic rings from 18 Wistar rats; the rings were suspended in aerated Krebs solution. Changes in isometric tension were measured to increasing concentrations of alphaalphaHb (1.8 x 10(-9) to 10(-4) M) on phenylephrine (PE)-induced contraction (3 x 10(-7) M), on acetylcholine (ACh)-induced relaxation (10(-8) to 10(-6) M), on SNP-induced relaxation (10(-9) and 10(-8) M), and on PE-induced contraction with an endothelin-1 (ET1) receptor antagonist, BQ123 (10(-5) M). Control rings received no alphaalphaHb. A concentration-dependent increase of the PE-precontraction (1.3%, 6.8%, 17.4%, and 34%, respectively) as well as the inhibition and reversal of ACh-induced relaxation was observed after alphaalphaHb. The presence of alphaalphaHb decreased the SNP-induced relaxation in the presence or absence of endothelium. The relaxation induced by SNP was reduced with time in the presence, but not in the absence, of alphaalphaHb. In conclusion, although pharmacological modulation of the vasoconstriction is possible with nitric oxide donors, our findings suggest that in the clinical setting, large sustained donor doses may be required.

Animals↗

PubMed2000

Increased nitric oxide synthase activity and expression in the human uterine artery during pregnancy.

Evidence exists that NO plays a role in the vasodilation that occurs during pregnancy. The purpose of the present study was to determine whether the role of NO is associated with an increase in the activity and protein expression of NO synthase (NOS) in the human uterine artery. Uterine arteries were obtained from pregnant patients (P arteries) and nonpregnant patients (NP arteries). NOS activity was estimated with the L-[(3)H]-arginine-to-L-[(3)H]-citrulline conversion method and on the basis of changes in tissue levels of cGMP. Western immunoblotting and immunohistochemistry were used to assess NOS protein expression. Ca(2+)-dependent NOS activity was 8 times greater (P:<0.01) in P than in NP arteries. Although most of this pregnancy-induced increase in NOS activity was Ca(2+) dependent (64%), a considerable portion was Ca(2+) independent. Expressions of endothelial NOS (eNOS) and neuronal NOS, but not inducible NOS, were demonstrated in P and NP arteries. The eNOS was located in the endothelium and stained with a qualitative order of P arteries>NP arteries (follicular)>NP arteries (luteal). The neuronal NOS was located in the adventitia of P and NP arteries. Basal NO-dependent and bradykinin-stimulated levels of cGMP were higher (P:<0.05) in P than in NP arteries. These results indicate that an upregulation of eNOS protein expression could account for the increased NO synthesis/release in the human uterine artery during pregnancy.

Adult↗

PubMed2000

A role for nitric oxide in endotoxin-induced depletion of the peripheral catecholamine stores.

Endotoxemia is associated with increased sympathetic nerve activity and depletion of norepinephrine (NE) and epinephrine (EPI) contents in the adrenal gland and in sympathetically innervated tissues. Endotoxin (bacterial lipopolysacchride [LPS]) causes an increased production of nitric oxide (NO) by inducing nitric oxide synthase (iNOS) expression in various tissues. This increased production of NO contributes significantly to the hypotension associated with endotoxemia. At high concentrations, NO also can act as a neurotoxin. In this study we tested the hypothesis that increased production of NO is involved in depletion of catecholamine content in various tissues from rats treated with a nonlethal dose of LPS. Catecholamine content was measured by high-performance liquid chromatography with electrochemical detection (HPLC-EC) and NOS activity was measured by the 3H-I-arginine to 3H-I-citrulline conversion method. The NE content was decreased in rat adrenal gland, lung, spleen, tail artery, and aorta after LPS. The maximal decrease was at 24 h and returned to control levels at 6 days (144 h). There was no depletion of the NE content in the heart. The EPI content in the adrenal gland was greatly depleted (91%) from 12 to 72 h after LPS. LPS increased the NOS activity in all tissues examined. The time course for NOS activity showed an increase at 3 h, a further increase at 6 h, and a return to control level at 48 h after LPS. The increase in NOS activity occurred before maximal catecholamine depletion. Aminoguanidine, a relatively selective iNOS inhibitor, completely prevented NE depletion in all tissues and partially prevented adrenal EPI depletion induced by LPS. These results are consistent with the hypothesis that LPS-induced production of NO plays a role in depletion of tissue NE and EPI.

Adrenal Glands↗

PubMed1999

Regulation of adrenal angiotensin receptor subtypes: a possible mechanism for sympathectomy-induced adrenal hypertrophy.

OBJECTIVE: Previous studies indicate that the adrenal gland plays a compensatory role in the maintenance of blood pressure in chemically sympathectomized rats. However, the mechanisms responsible for compensatory adrenal responses are poorly understood. This study examined the regulation of adrenal growth and type 1 A, 1 B, and type 2 angiotensin II (Ang II) receptor (AT1A, AT1B and AT2) expression in the adrenal gland induced by sympathectomy. METHODS: Five-week-old male Sprague-Dawley rats were treated with either guanethidine (50 mg/kg per day, intraperitoneally) or vehicle for 5 weeks. Norepinephrine and epinephrine levels in the atrium of the heart were measured by high-pressure liquid chromatography. Plasma renin activity was determined by radioimmunoassay. Adrenal AT1 and AT2 receptor density was determined by radioligand binding assay. Adrenal AT1A, AT1B and AT2 mRNA levels were determined by Northern blot analysis. RESULTS: Norepinephrine and epinephrine levels in the atrium of the heart were decreased 86% (P < 0.0001) and 58% (P < 0.05) by guanethidine treatment, respectively. Plasma renin activity was decreased 71% (P< 0.001) in guanethidine-treated rats compared with vehicle. In contrast, the ratio of adrenal to body weight was increased 38% in guanethidine-treated rats compared with vehicle (P< 0.001). Adrenal AT1 and AT2 receptor density was increased by guanethidine treatment (P< 0.05). Adrenal mRNA levels for AT2 (P< 0.001) and AT1A (P< 0.01), but not AT1B (P>0.05), were increased in guanethidine-treated rats compared with vehicle (P< 0.01). There were positive correlations between adrenal weight and AT2 (r = 0.9, P< 0.001) and AT1A (r = 0.6, P< 0.05) but not AT1B (r = - 0.01, P > 0.05) expression. CONCLUSIONS: Impairment of the sympathetic nervous system with guanethidine withdraws the normal stimulation of this system on the circulating renin-angiotensin system, but upregulates the expression of adrenal Ang II receptors. Increased expression of adrenal AT2 and AT1A receptors may play an important role in adaptive adrenal hypertrophy and hormonal responses to sympathectomy.

Adrenal Glands↗

PubMed1998

Pregnancy augments nitric oxide-dependent dilator response to acetylcholine in the human uterine artery.

The influence of pregnancy on the dilator effects of acetylcholine in the isolated human uterine artery was investigated. Acetylcholine (0.1 nM to 0.1 microM) produced concentration- and endothelium-dependent relaxation of norepinephrine (3 microM)-induced contraction. The relaxation was greater in arteries from pregnant patients (P arteries) than from non-pregnant patients (NP arteries). The maximal relaxation was 53.5+/-3.4% (n=21) in P arteries and 23.5+/-2.5% (n=35) in NP arteries. In both P and NP arteries the cholinergic relaxation was increased in the presence of superoxide dismutase and greatly reduced in the presence of the nitric oxide synthase inhibitors, NG-mono-methyl L-arginine (L-NMMA) and L-nitro-arginine-methylester (L-NAME). The effect of these nitric oxide synthase inhibitors was reversed by L-arginine. We conclude that pregnancy enhances acetylcholine-induced nitric oxide synthesis and release in the human uterine artery.

Acetylcholine↗

PubMed1997

Regulation of type 1 ANG II receptor in vascular tissue: role of alpha1-adrenoreceptor.

Angiotensin II (ANG II) and norepinephrine (NE) are important regulators of vascular function and structure. Recent studies showed that there are multiple interactions between these two potent vasoconstrictor agents. The present experiment was designed to investigate the effect of NE on the expression of the type 1 ANG II receptor (AT1) in the aorta and cultured vascular smooth muscle cells (VSMC) of rats. Rats were subcutaneously infused with either NE (0.5 microg x kg(-1) x min(-1), n = 6) or the alpha1-adrenoreceptor antagonist prazosin (3.5 microg x kg(-1) x min(-1), n = 6) for 2 wk. Body weight and tail cuff systolic blood pressure were not modified compared with the vehicle control (P > 0.05). Northern blot analysis showed that AT1 mRNA levels in aorta were decreased by 38% in NE-treated rats and increased 117% in prazosin-treated rats (P < 0.05) compared with control. To determine whether NE directly regulates expression of vascular AT1 mRNA and AT1 receptor density, Northern blot analysis and radioligand binding experiments were performed in cultured VSMC. Incubation of VSMC with NE (10(-7) M) led to 44% decrease in AT1 mRNA levels (P < 0.05) and 39% decrease in AT1 receptor density (P < 0.05). Prazosin, but not the alpha2-adrenoreceptor antagonist yohimbine, prevented NE-induced decrease in AT1 mRNA and AT1 receptor density in these cells. Taken together, our results indicate that vascular AT1 gene expression and receptor protein are regulated by ambient NE levels, and NE-induced downregulation of AT1 mRNA and receptor protein is mediated, at least in part, by activating alpha1-adrenoreceptors.

Adrenergic alpha-Agonists↗

PubMed1996

Differential effects of prolonged septicemia on isolated pulmonary arteries and veins from sheep.

Isolated third-order pulmonary arteries and veins from sheep were examined for the effects of septicemia on norepinephrine-induced contractions, nitric oxide (NO)-mediated dilation, and basal cyclic GMP levels. The groups studied were as follows: control sheep (n = 7); sheep given live Pseudomonas aeruginosa (Ps, n = 6) for 48 h; and sheep given NG-mono-methyl-L-arginine during the last 24 h of Ps infusion (Ps-L-NMMA, n = 4). The norepinephrine-induced contractions were significantly greater (p < .05) in arteries from septic (Ps and Ps-L-NMMA) sheep. Basal cyclic GMP levels were similar in all of the arteries. The norepinephrine-induced contractions were significantly depressed (p < .05) in veins from septic (Ps and Ps-L-NMMA) sheep. Basal cyclic GMP levels in veins from Ps sheep were markedly elevated (p < .01). N omega-nitro-L-arginine methyl ester (L-NAME) ex vivo decreased cyclic GMP in both arteries and veins. Removal of endothelium enhanced contractions and decreased cyclic GMP in arteries and veins only from control sheep. The results show that septicemia differently affects the pulmonary artery and vein. The enhanced vasoconstriction of the artery is due to decreased endothelium-dependent NO release; the attenuated vasoconstriction of the vein is associated with NO-mediated increased cyclic GMP levels.

ADP Ribose Transferases↗

PubMed1996

Changes in regional hemodynamics after nitric oxide inhibition during ovine bacteremia.

We studied the action of nitric oxide synthase (NOS) inhibition on changes in regional blood flow during a continuous infusion of live bacteria. Eighteen ewes were chronically instrumented. After a 7-day recovery period, an infusion of 10(6) colony-forming units/min Pseudomonas aeruginosa was begun. At 24 h, cardiac output increased significantly above baseline in all groups (5.9 +/- 0.4 vs. 8.2 +/- 0.6 l.min 1.m-2), systemic vascular resistance decreased (1,362 +/- 120 vs. 821 +/- 145 dyn.g.cm-5.m-2), and cerebral, cephalic mesenteric, and hindlimb blood flows increased. The animals were then equally and randomly assigned to a bolus of a NOS inhibitor, either 25 mg/kg N omega-nitro-L-arginine methyl ester (L-NAME) or 20 mg/kg N omega-monomethyl-L-arginine (L-NMMA), followed by a continuous infusion of 7 mg.kg-1.min-1 L-NMMA or saline. After NOS inhibition, cardiac index decreased [5.6 +/- 0.1 (L-NAME) and 5.5 +/- 0.4 l.min-1.m-2 (L-NMMA)] and remained significantly decreased for 12 h. 1-NAME decreased carotid and mesenteric blood flows to 64% of the preseptic baseline, and they remained below baseline for 20 h. L-NMMA decreased blood flows only to preseptic baseline values. NOS inhibitors may affect blood flows independently of their hemodynamic effects.

Animals↗

PubMed1995

Pregnancy-induced alterations of neurogenic constriction and dilation of human uterine artery.

The responses to electrical field stimulation (EFS) of perivascular nerves in human uterine arteries were characterized. The arteries were removed from pregnant and nonpregnant patients undergoing hysterectomy. Tetrodotoxin, guanethidine, and phentolamine blocked EFS (2 min, 80 V, 0.1-ms duration)-induced constriction. The constrictions and the endogenous norepinephrine levels were lower (P < 0.01) in uterine arteries from pregnant than from nonpregnant patients. When arterial rings were precontracted, the response to EFS was biphasic, consisting of an initial constriction followed by a postconstriction relaxation. The EFS-induced relaxation was endothelium independent and was greater (P < 0.01) in uterine arteries from pregnant than from nonpregnant patients. The relaxation was enhanced by guanethidine and superoxide dismutase, inhibited by nitric oxide synthase inhibitors, blocked by tetrodotoxin, and unaffected by atropine, propranolol, or indomethacin. The results demonstrate that human uterine arteries respond to EFS with contraction and relaxation and that these responses may be mediated, respectively, by norepinephrine and, in part, by nitric oxide released from periarterial nerves. The decrease in neuronally mediated uterine arterial constriction and the increase in dilation could be physiological mechanisms for ensuring appropriate uteroplacental perfusion.

Adult↗

PubMed1994

Isolated, perfused rabbit ear artery: a model for studying segmental vasoconstriction and dilatation.

Severe increases in blood pressure (BP) are associated with a segmental pattern of constriction and dilatation in small arteries and arterioles, but the pathogenesis is poorly understood. We showed that the isolated, perfused rabbit ear artery typically develops segmental constriction and dilatation when intraluminal pressure is > 160-180 mm Hg during field stimulation of perivascular nerves (> 6 Hz) or extra- or intraluminal infusions of norepinephrine (NE > 10(-7) M) or phenylephrine (PE) (> 5 x 10(-7) M). Light, transmission, and scanning electron microscopy showed that the dilated vessel segments initially show endothelial injury with no smooth muscle lesions. After repeated or prolonged exposure to high intraluminal pressure, dilated segments manifest extensive and severe endothelial and smooth muscle damage. Dilated regions also became abnormally permeable to tracer particles (ferritin). Constricted segments did not show evidence of endothelial or smooth muscle injury or hyperpermeability. These changes, i.e., segmental vasoconstriction/dilatation, hyperpermeability, and vessel wall damage localized to dilated segments, are comparable to those that occur in small arteries and arterioles during severe hypertension. We discuss the potential usefulness of the isolated ear artery as a model for studying the pathogenesis and morphology of segmental vasoconstriction/dilatation.

Animals↗

PubMed1993

Relaxation by calcitonin gene-related peptide may involve activation of K+ channels in the human uterine artery.

The vasodilatory role of calcitonin gene-related peptide in activating K+ channels was examined in isolated, suffused human uterine arteries. Calcitonin gene-related peptide produced a concentration-dependent relaxation of norepinephrine (1 microM)-induced contractions. Calcitonin gene-related peptide was antagonized by glybenclamide (1-100 microM), an inhibitor of ATP-sensitive K+ channels, but not by tetraethylammonium (1 mM), an inhibitor of calcium(2+)-activated K+ channels. Glybenclamide (10 microM) produced a 6.7 fold and an 11-fold shift to the right of calcitonin gene-related peptide (0.1 to 100 nM) in uterine arteries from pregnant patients (n = 3) and nonpregnant patients (n = 6), respectively. Calcitonin gene-related peptide (10 nM) less effectively (P < 0.05) relaxed contractions produced by KCl (50 mM) (29.4 +/- 1.6%) than by norepinephrine and glybenclamide (10 microM) did not reverse this relaxation (22.2 +/- 6.8%, n = 4 nonpregnant patients). Pinacidil (1 microM), an ATP-sensitive K+ channel opener, relaxed norepinephrine-induced contractions of uterine arteries. Glybenclamide (10 microM) also antagonized pinacidil. These results suggest that calcitonin gene-related peptide relaxes norepinephrine-contracted human uterine arteries, at least in part, by activation of a K+ channel, perhaps of the ATP-sensitive type.

Adenosine Triphosphate↗

PubMed1993

Possible physiologic role of calcitonin gene-related peptide in the human uterine artery.

OBJECTIVE: The purpose of our study was to determine the potential physiologic role of calcitonin gene-related peptide as an endogenous vasodilator of human uterine arteries during pregnancy. STUDY DESIGN: Isolated, suffused uterine arteries from pregnant patients (n = 9) and nonpregnant patients (n = 19) were used in the study. RESULTS: Calcitonin gene-related peptide (1 nmol/L to 0.1 mumol/L) produced a concentration-dependent relaxation of norepinephrine (1 mumol/L)-induced contractions. The values of calcitonin gene-related peptide that inhibited norepinephrine-induced contractions by 50% were 0.9 +/- 0.7 nmol/L (n = 8) and 6.5 +/- 1.5 nmol/L (n = 12) in pregnant and nonpregnant arteries, respectively. The calcitonin gene-related peptide-induced relaxation was not affected by propranolol (1 mumol/L), indomethacin (5 mumol/L), methylene blue (10 mumol/L), or by the removal of the endothelium. The relaxant effect of calcitonin gene-related peptide was inhibited by human calcitonin gene-related peptide(8-37). The endogenous levels of calcitonin gene-related peptide were 110.2 +/- 13.5 pmol/L/gm wet weight in pregnant arteries and 14.8 +/- 3.2 pmol/L/gm wet weight in nonpregnant arteries. CONCLUSIONS: These results demonstrate that the vasodilatory effect of calcitonin gene-related peptide is mediated by calcitonin gene-related peptide1 receptors and does not involve beta-adrenoceptors, vasodilator prostanoids, increased levels of guanosine 3',5'-cyclic monophosphate, or endothelium-derived relaxing factor. The findings that calcitonin gene-related peptide acts as a potent dilator and that pregnancy increases both the sensitivity to calcitonin gene-related peptide and the endogenous levels of calcitonin gene-related peptide support the view that calcitonin gene-related peptide has a physiologic role in dilating the uterine vasculature, especially during pregnancy.

Adult↗

PubMed1993

Quality assurance in the department of pediatrics. An application of quality management.

A continuous quality improvement program can provide the means through which medical organizations can guide their activities. This article illustrates how a pediatrics department in an urban medical center incorporated continuous quality improvement into the management of health services. Key elements of the Quality Assurance program included the organization and facilities in the department of pediatrics, important processes related to patient care, and outcome measures. If a structure is established that allows participation in decision-making and mutual adjustment, trained professionals can perform up to their standards and those standards of their peers. Involvement of physicians in the design of quality management programs and other administrative strategies offer an opportunity to develop a working formula for ongoing success.

Adolescent↗

PubMed1992

Lack of reactivity of uterine arteries from patients with obstetric hemorrhage.

Obstetric hemorrhage may occur throughout pregnancy and the puerperium. The purpose of this study was to investigate the reactivity of isolated, suffused uterine arteries from obstetric patients with uncontrollable uterine bleeding and to compare those blood vessels with uterine arteries from patients undergoing cesarean hysterectomy for other medical reasons (control patients). The uterine arteries from the control patients (n = 9) responded with maximal or near-maximal constriction to norepinephrine (30 mumol/L, 3.6 +/- 1 gm), potassium chloride (75 mmol/L, 10.2 +/- 3 gm), prostaglandin F2 alpha (30 mumol/L, 1.8 +/- 1 gm), and arginine vasopressin (1 mumol/L, 18.8 +/- 2.6 gm). In uterine arteries from five patients with uncontrollable bleeding, the constrictor responses to the same drugs were markedly depressed: norepinephrine (30 mumol/L, 0.5 +/- 0.2 gm), potassium chloride (75 mmol/L, 1.9 +/- 0.8 gm); prostaglandin F2 alpha (30 mumol/L, 0 gm), and arginine vasopressin (1 mumol/L, 0.2 +/- 0.05 gm). Uterine arteries from two patients exhibited no constrictor responses to norepinephrine (30 mumol/L), potassium chloride (75 mmol/L), prostaglandin F2 alpha (30 mumol/L), or arginine vasopressin (1 mumol/L). The impaired responses to the vasoconstrictor drugs were not reversed by indomethacin (1 mumol/L), which is an inhibitor of prostaglandin synthetase; methylene blue (10 mumol/L), which is a blocker of endothelium-derived relaxing factor activation of guanylate cyclase; or propranolol (1 mumol/L), a beta-adrenergic receptor antagonist. The levels of adenosine 3':5'-cyclic monophosphate were not elevated in the uterine arteries from the patients with obstetric hemorrhage. The impaired reactivity to the multiple vasoconstrictors implies that a mechanism involved in constriction common to all of the constrictors is depressed or blocked. Furthermore, the depression or lack of reactivity of these isolated uterine arteries is not mediated by vasodilatory prostaglandins, endothelium-derived relaxing factor, beta-adrenergic receptors, or elevated levels of adenosine 3':5'-cyclic monophosphate. The results suggest that obstetric hemorrhage involves, in part, a lack of constrictor reactivity of the uterine vasculature.

Adult↗

PubMed1992

An overview of mental health services for American Indians and Alaska Natives in the 1990s.

Native Americans appear to be at higher risk than other U.S. ethnic groups for mental health problems, including depression, substance abuse, domestic violence, and suicide. Despite recent increases in the federal budget for mental health services for Native Americans, less than 50 percent of the estimated need for ambulatory services is being met. Initiatives to improve the quantity and quality of mental health services for Native Americans in the 1990s include development of a national mental health plan, increased technical assistance to Native American communities, additional training and research, and continued attention to standards that promote high-quality, culturally relevant care. Tribes themselves are seen as the most appropriate locus for initiation of programs for preventing emotional problems in their communities.

Community Mental Health Services↗

PubMed1991

Magnesium sulfate-induced relaxation of uterine arteries from pregnant and nonpregnant patients.

The effects of magnesium sulfate at different concentrations were investigated in isolated rings of uterine arteries from pregnant and nonpregnant patients. Addition of magnesium sulfate (0.5 to 9.6 mmol/L) to the suffusion medium containing the normal concentration of 1.2 mmol/L magnesium sulfate produced concentration-dependent relaxation of norepinephrine (1 mumol/L)-induced or potassium chloride (35 mmol/L)-induced contractions. Magnesium sulfate was about three times more potent in causing inhibition of potassium chloride-induced contractions in uterine arteries from pregnant patients than in those from nonpregnant patients. The concentrations that inhibited 50% of the contraction induced by potassium chloride were 0.6 +/- 0.2 mmol/L (n = 4) in the arteries from pregnant patients and 1.6 +/- 0.2 mmol/L (n = 4) in the arteries from nonpregnant patients. At high concentrations (4.8 and 9.6 mmol/L), magnesium sulfate also was more potent in inhibiting norepinephrine-induced contractions in arteries from pregnant women than in arteries from nonpregnant women. The magnesium sulfate-induced relaxation was almost completely inhibited by calcium chloride (2 mmol/L) added to the suffusion medium containing the normal concentration of 2.5 mmol/L calcium chloride but was not affected by indomethacin (5 mumol/L), methylene blue (10 mumol/L), or removal of the endothelium. The results show that magnesium sulfate, at therapeutic blood concentrations, acts as a potent dilator of human uterine arteries, especially those from pregnant patients. The results are consistent with the view that magnesium sulfate may facilitate uteroplacental perfusion.

Adult↗

PubMed1990

Cocaine inhibits baroreflex control of blood pressure by actions at arterial baroreceptors.

Blood pressure and heart rate often increase during cocaine intoxication, but the mechanisms of these cardiovascular responses are poorly understood. The most often suggested theories are central nervous system mechanisms involving the blockade of neuronal transmitter uptake. Cocaine also has potent local anesthetic properties, and in this study we tested the possible role of peripheral actions of cocaine at baroreceptor afferents. Single fiber baroreceptors were recorded using an in vitro preparation of the rat aortic arch. Diameter, pressure, and baroreceptor discharge were recorded. Cocaine perfused through the lumen of the aortic arch at a suprathreshold pressure reduced baroreceptor discharge within 90 s of entering the lumen of the aorta. Slow ramps of pressure elicited complete pressure- and diameter-discharge curves every 5 min. Beginning at about 1 microM, cocaine inhibited baroreceptor function; threshold increased, the maximum discharge decreased, and at 100 microM cocaine, all discharge ceased. The vasodilator nitroprusside or the alpha 1-adrenoreceptor antagonist prazosin did not affect baroreceptor responses to cocaine. In in vivo tests in rabbits, cocaine that perfused through a vascularly isolated carotid sinus reduced the slope of the baroreflex relationship between carotid sinus pressure and systemic mean arterial pressure. Significant depression of baroreceptor function was found at concentrations similar to the plasma cocaine levels measured in clinical studies. The local anesthetic properties of cocaine may be involved in baroreceptor effects. Our studies suggest a possible contributing role of a new site of action of cocaine outside the central nervous system. Compromise of baroreceptor reflexes could facilitate the development of serious cardiovascular complications associated with cocaine abuse.

Animals↗

PubMed1989

Values and priorities: their effect on knowledge utilization in public mental health programs.

Developing and maintaining shared values and priorities in public mental health systems is crucial to clinical, program, policy and administrative success. The issues of establishing priority populations, mobilizing resources, and improving quality of care and personal leadership style are discussed as examples of the ways in which such consensus contributed to progress in Pennsylvania's public mental health system.

Health Planning↗