Biomedical subjects

A K Johnson

Publications and source records attributed to A K Johnson.

At least 109 records · Page 6Linked to original sources

PubMed1994

Enhanced bradycardia but not renal sympathoinhibition during hemorrhage in rats with area postrema lesions.

Hypotensive hemorrhage inhibits renal sympathetic nerve activity (SNA) and heart rate (HR) in rats. The area postrema (AP) is reported to modulate autonomic responses to arginine vasopressin (AVP) and may be a site where circulating AVP influences SNA and HR during hypotensive hemorrhage. We found a similar renal sympathoinhibition in AP-lesioned (APX) and sham-lesioned (Sham) rats during hypotensive hemorrhage and a greater bradycardia in APX compared with Sham rats. Further inhibition of renal SNA with AVP infusion was not observed in APX rats, although the bradycardic action of AVP infusion was comparable to that in Sham rats. Thus the AP attenuates bradycardia but not renal sympathoinhibition during hypotensive hemorrhage in normal rats. Nonetheless, an intact AP permits further reduction in renal SNA during infusion of AVP. If AVP contributes to hypotensive hemorrhage-induced renal sympathoinhibition, its action may occur at sites other than the AP or at the AP where such action is counterbalanced by sympathoexcitatory factor(s) also activated during hypotensive hemorrhage. Finally, enhanced bradycardia during hypotensive hemorrhage in APX rats suggests it may not be the site of action for AVP-induced bradycardia in intact rats.

Animals↗

PubMed1994

Renin-angiotensin, arterial blood pressure, and salt appetite in rats.

Simultaneous administration of the diuretic furosemide (10 mg/kg sc) and a low dose of the angiotensin-converting enzyme inhibitor captopril (5 mg/kg sc) reduced mean arterial blood pressure (MAP) and increased ingestion of water and 0.3 M NaCl within 2 h. Administration of either agent alone did not reduce MAP or cause significant fluid intakes. The increased ingestion of water and saline after furosemide plus captopril 1) was not due to increased excretion of water and sodium compared with losses after furosemide alone, 2) was abolished by the AT1-receptor blocker, losartan (10 mg/kg sc), and 3) was abolished by administration of a greater dose of captopril (100 mg/kg sc). Intravenous infusion of phenylephrine (3-4 micrograms.kg-1 x min-1) prevented the reduction in MAP after furosemide plus captopril and blunted the saline intake but not water intake. Simultaneous administration of the vasodilator minoxidil and captopril also stimulated robust salt appetite in association with reduced MAP. It is concluded that the integrity of renin-angiotensin mechanisms is necessary for the rapid ingestion of water and saline after furosemide and captopril and that arterial pressure modulates the behavioral responses.

Angiotensin Receptor Antagonists↗

PubMed1994

Effects of sinoaortic baroreceptor denervation on depletion-induced salt appetite.

This study examined the effects of denervation of the carotid sinus and aortic arch baroreceptors on sodium depletion-induced salt appetite in rats. Depletion of extracellular fluid began with two injections of furosemide (10 mg/kg sc), 30 min apart, and removal of all ambient sodium from the cages. Water and sodium-deficient chow were available overnight. The next morning, access to 0.3 M NaCl was provided, and intakes of water and saline were measured every 30 min for 2 h and again at 24 h. Three such tests were administered. Groups of sham and sinoaortic baroreceptor-denervated (SAD) rats had equivalently negative water and sodium balances before access to saline the next morning. Sham-denervated rats drank sufficient saline in 2 h to achieve positive sodium balance and subsequently ingested sodium in excess of need for another 22 h. SAD rats drank half as much saline as sham-denervated rats by 2 and 24 h and remained in negative balance at 2 h. Sham-denervated rats increased their intakes of saline solution with repeated tests, but SAD rats did not. These findings suggest that arterial baroreceptors provide critical neural input for the normal expression of salt appetite.

Animals↗

PubMed1994

Endocrine changes associated with a rapidly developing sodium appetite in rats.

Simultaneous administration of the diuretic furosemide (10 mg/kg) and a low dose of the angiotensin-converting enzyme (ACE) inhibitor captopril (5 mg/kg) results in short-latency thirst and sodium appetite (i.e., the rapid ingestion of water and NaCl solution). To elucidate potential mechanisms for mediating this behavior, changes in plasma levels of key hormones involved in fluid intake and balance were characterized in rats subjected to this treatment protocol. Rats treated jointly with furosemide and low-dose captopril had exaggerated increases in plasma renin activity and angiotensin I but equivalent increases in plasma aldosterone compared with rats treated with either agent alone. Treatment with furosemide plus low-dose captopril increased plasma vasopressin but not plasma oxytocin. The administration of a higher dose of captopril (100 mg/kg) with furosemide, a combination of drugs that does not stimulate fluid intake (29), further increased plasma renin activity and angiotensin I but prevented the rise in plasma vasopressin. The results support the hypothesis that thirst and salt appetite generated by this protocol depend on angiotensin II formed within brain circumventricular organs rather than the systemic circulation.

Aldosterone↗

PubMed1994

Intracerebroventricular insulin produces nonuniform regional increases in sympathetic nerve activity.

Insulin has been shown to increase sympathetic nerve activity (SNA). Although it has been proposed that insulin acts within the central nervous system (CNS) to increase sympathetic neural outflow, there is little evidence for direct central neural sympathoexcitatory effects of insulin. To determine whether intracerebroventricular insulin elicits increases in peripheral SNA, we infused insulin (0.1 microU/min, low; 10 microU/min, medium; and 100 microU/min, high doses) or artificial cerebrospinal fluid (aCSF) into the third cerebral ventricle of chloralose-anesthetized Wistar rats while recording lumbar SNA. In separate animals, 10 microU/min of insulin were infused while recording adrenal SNA and renal SNA. Blood glucose and plasma insulin levels did not significantly change during intracerebroventricular infusion of insulin. Lumbar SNA, expressed as percentage of baseline, did not change in rats infused with aCSF (+ 13% +/- 8%) but increased significantly in rats infused with low (+ 72 +/- 17%), medium (+ 119 +/- 30%), and high (+ 113 +/- 25%) doses of insulin (P < 0.05). Intracerebroventricular insulin failed to significantly increase adrenal SNA or renal SNA. Blood pressure and heart rate did not change during insulin infusion. The results indicate that administration of insulin into the third cerebral ventricle produces regionally nonuniform increases in sympathetic neural outflow in the absence of changes in blood glucose or plasma insulin.

Adrenal Glands↗

PubMed1994

Dissociation between vasopressin and oxytocin mRNA and peptide secretion after AV3V lesions.

The effect of hypertonic NaCl consumption on vasopressin (VP) and oxytocin (OT) mRNA levels and plasma and pituitary peptides was evaluated in rats with sham or anterior ventral third ventricular (AV3V) lesions. Rats were given tap water or 2% NaCl for 4 days. Because the rats with lesions drank significantly less salt solution than the controls (78.8 +/- 17.4 vs. 205.5 +/- 37.8 ml/4 days), a second control group was included in which saline intake was matched to the lesioned group. AV3V rats showed a deficit in the peptide response to the osmotic stimulus. There was no increase in plasma VP or OT or decrease in posterior pituitary peptide content in the face of an extreme hypernatremia: plasma sodium of 180.1 +/- 4.2 meq/l. Evaluation of mRNA changes by means of in situ hybridization showed that animals with lesions responded to the salt challenge with increases in hypothalamic VP and OT mRNA levels. There were significant increases in paraventricular and supraoptic OT mRNA and paraventricular VP mRNA in the lesioned group. The salt-matched control group showed no changes in peptide mRNA levels. These results demonstrate that AV3V lesions produce an impairment of the salt-neuroendocrine reflex but a persistence of the peptide mRNA response. Differences in control mechanisms must account for this dissociation between peptide mRNA expression and peptide secretion.

Animals↗

PubMed1994

Anteroventral third ventricle lesions abolish lumbar sympathetic responses to insulin.

Insulin has been shown to increase sympathetic nerve activity. Because evidence shows that insulin acts within the central nervous system, we hypothesized that lesions of the anteroventral third ventricle region, an area rich in insulin receptors, would abolish sympathetic responses to hyperinsulinemia. We measured mean arterial pressure and lumbar sympathetic nerve activity in fasted, anesthetized sham-lesioned (n = 8) and lesioned (n = 8) rats before and after intravenous insulin infusion at 0.13 U/h during euglycemic clamp. Additional sham-lesioned (n = 10) and lesioned (n = 5) rats received vehicle infusion. Insulin-infused sham-lesioned rats had substantially greater increases in lumbar sympathetic nerve activity (+83 +/- 18%) than vehicle-infused sham-lesioned rats (+27 +/- 4%). Most importantly, insulin-infused lesioned rats had increases in sympathetic activity (+32 +/- 11%) that were no greater than lesioned rats receiving vehicle (+23 +/- 16%). Blood pressure was not altered by insulin or vehicle. To test the possibility that lesions of the anteroventral third ventricle region nonspecifically suppress sympathetic excitatory responses, we evaluated reflex increases in lumbar sympathetic activity to nitroglycerin in sham-lesioned (n = 5) and lesioned (n = 8) rats. Rats with lesions and sham lesions showed comparable increases in lumbar nerve activity during nitroglycerin-induced hypotension. In summary, increases in sympathetic nerve activity to intravenous insulin infusion are abolished by anteroventral third ventricle lesions. These data indicate that the integrity of this brain region is necessary for activation of lumbar sympathetic nerve activity by systemic administration of insulin.

Animals↗

PubMed1994

Nitrosyl factors mediate active neurogenic hindquarter vasodilation in the conscious rat.

Exposure to noxious environmental stimuli such as air-jet stress (AJS) produces a pattern of hemodynamic changes referred to as the "defense reaction". In the rat these changes include a relatively modest increase in mean arterial blood pressure (MAP), tachycardia, renal and mesenteric vasoconstriction, and a marked hindquarter vasodilation. The aim of the present study was to determine whether the AJS-induced decrease in hindquarter resistance is mediated by a sympathetic neurogenic vasodilator system that uses nitric oxide (NO) and/or related nitrosyl factors. AJS produced a small, rapid increase in MAP, which quickly returned to baseline (within 5 seconds), and a substantial increase in hindquarter blood flow and decrease in hindquarter resistance, which occurred almost instantaneously (1 to 2 seconds) and were sustained for at least 30 seconds. The intravenous injection of either bretylium (5 mg/kg), which prevents impulse propagation-mediated release of neurotransmitters/neuromodulators from sympathetic terminals, or NG-nitro-L-arginine methyl ester (L-NAME, 25 mumol/kg), which blocks NO synthesis, essentially abolished the AJS-induced increase in hindquarter blood flow and fall in hindquarter resistance. In contrast, the hindquarter vasodilation produced by the NO donor sodium nitroprusside (4 micrograms/kg i.v.) was markedly exaggerated in the bretylium- or L-NAME-treated rats. We also found that rat lumbar sympathetic fibers projecting to the hindquarter vasculature contain NADPH diaphorase, a marker for NO synthase in paraformaldehyde-perfused tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Cardiovascular effects produced by systemic injections of nitro blue tetrazolium in the rat.

Nitro blue tetrazolium is a powerful electron acceptor which is widely used to localize NADPH-dependent flavin-containing enzymes known as NADPH diaphorases. By accepting electrons, nitro blue tetrazolium is known to inhibit the activity of these enzymes. The present study examined the effects of intravenous nitro blue tetrazolium on arterial blood pressure and regional blood flows in urethane-anesthetized rats. Nitro blue tetrazolium (0.1-5 mol/kg) produced a dose-dependent hypotension and differential effects on regional hemodynamics including decreases in hindquarter and mesenteric vascular resistances and a marked increase in renal resistance. These results demonstrate that systemic administration of nitro blue tetrazolium produces profound hemodynamic effects, the mechanisms of which remain to be elucidated.

Anesthesia↗

PubMed1993

2,5-Dimethoxy congeners of (+)-and (-)-3-(3-hydroxyphenyl)-N-n- propylpiperidine.

p-Dimethoxyaryl analogs of certain potent catechol-derived dopaminergic agonists show dopaminergic properties for which no structure-activity relationship has yet been defined. (S)-3-(3-Hydroxyphenyl)-N-n-propylpiperidine (1, S-"3-PPP") is a dopaminergic autoreceptor agonist, and at high doses it also exhibits postsynaptic antagonism. (R)-1 is a postsynaptic agonist. In a continuation of studies of effects of the p-dimethoxy moiety at dopamine receptors, synthesis and resolution of the 2,5-dimethoxy analog 3 of 3-PPP was undertaken. The two enantiomers and the racemic modification showed cardiovascular effects consistent with actions at DA-2 receptors. The potency of all three compounds was much lower than that of 3-PPP, although they displayed approximately the same duration of action. Absolute configuration does not seem to be a major determinant of these compounds' ability to interact with DA-2 receptors.

Animals↗

PubMed1993

Afferent signaling and forebrain mechanisms in the behavioral control of extracellular fluid volume.

The body defends against reduced extracellular fluid volume both by activation of autonomic and endocrine reflexes and by mobilization of behavioral mechanisms. The behaviors that are required to correct an extracellular fluid deficit involve the ingestion of both water and sodium. It is reasonable to hypothesize that afferent neural input from both arterial and cardiopulmonary high pressure and volume receptors, and afferent humoral input in the form of ANG II, are important systemically-generated signals acting as afferent mediators of extracellular depletion-induced thirst and sodium appetite. Neural information from these signals has been shown to converge on forebrain structures located along the lamina terminalis where processing and integration of this input is likely to take place. This paper describes an analysis of the mechanisms of afferent signaling that accompanies a form of rapidly induced sodium appetite. Because volume and pressure-related input in concert with elevated activity of the renin-angiotensin system is likely to be important for generating this form of induced hypertonic sodium chloride and water intake, we have focused on the structures of the lamina terminalis, specifically the SFO, MnPO, and OVLT. Investigations that employ immunocytochemical methods for the detection of the early oncogene, c-fos, indicate that neurons in the lamina terminalis, as well as the SON and PVN, are activated by the composite of systemically derived signals necessary for producing thirst and sodium appetite. So far, there is no thorough understanding of how these visceral signals activate the neural substrates for these motivated behaviors. However, these studies, combining both functional and neuroanatomical approaches, provide a strategy for investigating the neurobiological basis of the behavioral and physiological control systems that maintain fluid balance and cardiovascular homeostasis. This paper describes an analysis of the mechanisms of afferent signaling that accompanies a form of rapidly induced sodium appetite. Because volume and pressure-related input, in concert with elevated activity of the renin-angiotensin system, is likely to be important for generating this form of induced hypertonic sodium chloride and water intake, we have focused on the structures of the lamina terminalis, specifically the SFO, MnPO, and OVLT. Investigations that employ immunocytochemical methods for the detection of the early oncogene, c-fos, indicate that neurons in the lamina terminalis, as well as the SON and PVN, are activated by the composite of systemically derived signals necessary for producing thirst and sodium appetite. So far, there is no thorough understanding of how these visceral sensory-related signals activate the neural substrates for these motivated behaviors.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed1993

Preparation and pharmacological evaluation of enantiomers of certain nonoxygenated aporphines: (+)- and (-)-aporphine and (+)- and (-)-10-methylaporphine.

The subject compounds were prepared as a part of a continuing structure-activity study of the contrasting actions (agonism-antagonism) of (+)- and (-)-11-hydroxy-10-methylaporphine at serotonin (5-HT1A) receptors. None of the targeted nonoxygenated aporphine derivatives demonstrated significant activity in assays for any effects at serotonin 5-HT1A receptors. It is concluded that, in the aporphine series, serotonergic agonist or antagonism requires an alkyl group ortho to a phenolic OH group in the A ring.

Animals↗

PubMed1993

Increases in cytosolic Ca2+ in rat area postrema/mNTS neurons produced by angiotensin II and arginine-vasopressin.

It is well established that neurons in the dorsal medulla, including the area postrema and the medial nucleus tractus solitarius (mNTS), are involved in the central actions of circulating peptides such as angiotensin II (ANG II) and arginine vasopressin (AVP). This report describes a preparation that permits the identification and maintenance of area postrema/mNTS neurons in culture in which the cellular and potentially subcellular responses to neurotransmitters and neuropeptides on area postrema/mNTS cells can be investigated. Following 15-21 days in culture, the effects of ANG II and AVP on changes in intracellular Ca2+ concentration ([Ca2+]i) were examined. Both ANG II and AVP resulted in a rapid and transient increase in [Ca2+]i reaching maximum in 15 s and returning towards baseline values within 180 s. The ANG II-mediated increase in [Ca2+]i was almost completely abolished by the selective angiotensin AT1 receptor subtype antagonist, losartan (DuP 753). These results suggest that ANG II and AVP modulate area postrema/mNTS neuronal activity by increasing intracellular Ca2+.

Angiotensin II↗

PubMed1993

Sensory circumventricular organs and brain homeostatic pathways.

Circumventricular organs (CVOs), small structures bordering the ventricular spaces in the midline of the brain, have common morphological and endocrine-like characteristics that distinguish them from the rest of the nervous system. Among their unique features are cellular contacts with two fluid phases--blood and cerebrospinal fluid--and neural connections with strategic nuclei establishing circuitry for communications throughout the neuraxis. A variety of additional morphological and functional characteristics of the CVOs implicates this group of structures in a wide array of homeostatic processes. For three of the circumventricular organs--the subfornical organ (SFO), the organum vasculosum of the lamina terminalis (OVLT), and the area postrema (AP)--recent findings demonstrate these structures as targets for blood-borne information reaching the brain. We propose that these three sensory CVOs interact with other nuclei in the maintenance of several homeostatic processes by way of neural and humoral links. We emphasize the collective role of brain CVOs in the maintenance of body fluid homeostasis as a model for the functional integration of these fascinating "windows of the brain" within central neurohumoral systems.

Animals↗

PubMed1993

Effects of carbonated and noncarbonated beverages at specific intervals during treadmill running in the heat.

Eight male runners performed four 2-hr treadmill runs at 65% VO2max in the heat (35 degrees C, 15-20% RH). A different beverage was offered each trial and subjects drank ad libitum for 2 min every 20 min. The beverages were, 6% carbohydrate (CHO) solution (NC 6), 6% carbonated-CHO solution (C 6), 10% CHO solution (NC 10), and 10% carbonated-CHO solution (C 10). NC 6 and C 6 contained 4% sucrose and 2% glucose. NC 10 and C 10 contained high fructose corn syrup. Subjects drank more NC 6 than C 6. Fluid consumption was not different among other trials. During all trials, volume consumed and % delta PV declined while heart rate and rectal temperature increased (p < 0.05). No significant differences occurred between beverages for these variables. Percent body weight lost was greater (p < 0.05) for the C 10 trial compared to the NC 6 trial. Neither sweat rate, percent fluid replaced, plasma [Na+], [K+], osmolality, percent of drink volume emptied from the stomach, or glucose concentration differed among trials. Plasma [K+] and osmolality increased (p < 0.05) over time. Ratings of fullness and thirst were not different among beverages, although both perceptions increased (p < 0.05) with time. It is concluded that (a) carbonation decreased the consumption of the 6% CHO beverage; (b) fluid homeostasis and thermo-regulation were unaffected by the solutions ingested; and (c) fluid consumption decreased with time, while ratings of fullness and thirst increased.

Adult↗

PubMed1993

Effects of arterial pressure on drinking and urinary responses to intracerebroventricular angiotensin II.

These experiments examined the dipsogenic responses of rats to intracerebroventricularly administered angiotensin II (ANG II) under normotensive and hypotensive conditions. Intravenous infusion of the vasodilator drug minoxidil (25 micrograms.kg-1.min-1), combined with the angiotensin converting enzyme inhibitor captopril (0.33 mg/min), both reduced blood pressure and prevented endogenous ANG II formation. Central infusions with ANG II (4 or 16 ng/h) began 60 min later, and the intravenous and intracerebroventricular infusions ran concurrently for another 90 min. Mean arterial pressure (MAP), water intake, urine volume (UV) and electrolyte excretion were measured throughout. Water intakes to both doses of intracerebroventricular ANG II were increased, and UV and electrolyte excretion were reduced during hypotensive conditions compared with normotensive conditions. Thus the increased water intakes occurred despite increased fluid retention. It is concluded that arterial hypotension enhances the dipsogenic effects of centrally administered ANG II, possibly through baroreceptor-mediated mechanisms.

Angiotensin II↗

PubMed1993

In vitro sensitivity of median preoptic neurons to angiotensin II, osmotic pressure, and temperature.

In vivo experiments suggest an interaction of the mechanisms involved in the regulation of body fluid balance and body temperature. Increases in plasma osmolality initiate drinking and increase the thermal set point for sweating. The median preoptic nucleus (MnPO) has anatomical connections with brain areas important in fluid balance and cardiovascular regulation and, with the preoptic-anterior hypothalamus, a thermoregulatory region. The present experiments employed in vitro single-unit recordings to determine the sensitivity of MnPO neurons to angiotensin II (ANG II), changes in osmotic pressure, and changes in temperature. One-fifth (11 of 55) of the MnPO neurons responded with changes in firing rate during the ANG II treatment, one-fourth (19 of 75) responded to changes in perfusate osmolality, and there was a significant effect of osmolality and ANG II on the thermosensitivity of 25% of the neurons tested.

Angiotensin II↗

PubMed1993

Rapid-onset "need-free" sodium appetite after lesions of the dorsomedial medulla.

Previous studies indicate the dorsomedial hindbrain is important in the maintenance of fluid balance. Lesions centering on the area postrema (AP) result in enhanced ad libitum intake of concentrated saline solutions on a 24-h basis as well as enhanced excretion of water and electrolytes. Additionally, rats with lesions of the AP are reported to have an exaggerated behavioral response to dipsogenic challenges that mimic depletion of the extracellular fluid compartment. In the studies reported here, we have observed that rats with lesions of the AP and immediately adjacent nucleus of the solitary tract consume large quantities of concentrated saline solutions within minutes of presentation. This intake does not appear to be related to sodium loss or depletion because the lesioned rats are in a positive sodium balance and the appetite persists after bilateral nephrectomy. These data, in conjunction with earlier studies, suggest that the dorsomedial medulla, including the AP, acts to prevent overconsumption of water and sodium that could result in increased extracellular fluid volume.

Animals↗