Search PubMed⌕ Search

Biomedical subjects

H K Jin

Publications and source records attributed to H K Jin.

36 records · Page 2Linked to original sources
PubMed1989

Central mechanisms of hypertension.

Central monoaminergic neurons, particularly noradrenergic neurons, are involved in the pathogenesis of hypertension. Dietary NaCl supplementation in NaCl-sensitive spontaneously hypertensive rats (SHR-S) elevates blood pressure, increases peripheral sympathetic nervous system activity, and depresses endogenous noradrenaline stores and noradrenaline release in the anterior hypothalamus (AHA). NaCl-resistant spontaneously hypertensive rats (SHR-R) and normotensive Wistar-Kyoto (WKY) rats are resistant to the NaCl-induced alterations in blood pressure and central and peripheral noradrenergic activity, whereas uninephrectomized Sprague-Dawley rats treated with DOCA + NaCl and Dahl-S rats receiving dietary NaCl supplementation develop NaCl-induced increments in blood pressure, but not depressed AHA noradrenaline release. The AHA is a major cardiovascular regulatory region, and depressor responses elicited by pharmacological (alpha 2-adrenoceptor) stimulation of this area are exaggerated in SHR-S fed a high NaCl diet compared to SHR-S fed a basal diet and SHR-R and WKY fed a high or basal NaCl diet. alpha 2-Adrenoceptors in the AHA are increased in number in SHR-S fed a high NaCl diet, presumably reflecting upregulation in response to reduced local noradrenaline release. These findings are consistent with the hypothesis that decreased noradrenergic activity of sympathoinhibitory neurons in the AHA may mediate the exacerbation in hypertension that occurs in SHR-S during dietary NaCl supplementation.

Animals↗
PubMed1989

Vasopressin lowers pulmonary artery pressure in hypoxic rats by releasing atrial natriuretic peptide.

The authors previously demonstrated that arginine vasopressin (AVP) lowers pulmonary artery pressure in rats with hypoxic pulmonary hypertension by activation of the V1 receptor. The pulmonary depressor effect of AVP in hypoxia-adapted rats is not due to its effect on cardiac output. The current study tested two alternative hypotheses: that AVP lowers pulmonary artery pressure in the hypoxia-adapted lung by (1) dilating pulmonary vasculature directly, or (2) releasing atrial natriuretic peptide (ANP) from the heart. The first hypothesis was tested by injecting AVP into the pulmonary arteries of isolated, buffer perfused lungs and monitoring pulmonary artery pressure, and by exposing preconstricted pulmonary artery rings to graded doses of AVP and monitoring the tension generated. AVP caused minimal vasodilation in perfused lungs and only a small vasodilator effect in pulmonary artery rings. The second hypothesis was tested by injecting AVP (160 ng/kg) or vehicle intravenously in conscious hypoxia-adapted (4 weeks) or air control rats and measuring ANP in arterial blood and atria, and by testing pretreatment with the V1 receptor antagonist d(CH2)5 Tyr(Me)AVP (130 micrograms/kg) on the AVP-induced increase in plasma ANP. AVP produced a 7-fold increase in plasma ANP (209 +/- 33 to 1346 +/- 233 pg/ml; p less than 0.05) in hypoxia-adapted rats and a 5-fold increase in ANP (122 +/- 22 to 573 +/- 174 pg/ml; p less than 0.05) in air controls. ANP release was abolished by pretreatment of both groups with d(CH2)5 Tyr(Me)AVP. The AVP-induced ANP release came mainly from left atrium. These data strongly suggest that the pulmonary depressor effects of AVP in hypoxia-adapted rats is due to augmented V1 receptor-induced release of ANP from left atrium.

Animals↗
PubMed1989

Atrial natriuretic peptide lowers pulmonary arterial pressure in patients with high altitude disease.

The authors' previous studies have demonstrated that IV administration of atrial natriuretic peptide (ANP) produces a dose dependent decrease in pulmonary arterial pressure in rats adapted to chronic hypoxia. To examine the effects of ANP on chronic hypoxic pulmonary hypertension in man, alpha-human ANP (200 micrograms) was infused (20 micrograms/min X 10 min) into the right atrium via a Swan-Ganz catheter in four patients with pulmonary hypertension of high altitude. Following the infusion, pulmonary arterial pressure fell gradually and remained depressed for 1 hour. Peak reductions in pulmonary arterial systolic pressure (PASP) and mean pulmonary arterial pressure (MPAP) were 23% and 30%, respectively. Systemic arterial pressure, cardiac output and cardiac index also tended to decrease, but these changes did not reach statistical significance. The data suggest that ANP is useful in the treatment of chronic hypoxic pulmonary hypertension in man.

Aldosterone↗
PubMed1989

Hemodynamic effects of arginine vasopressin in rats adapted to chronic hypoxia.

Acute and chronic pulmonary and systemic hemodynamic responses to arginine vasopressin (AVP) were examined in 4-wk hypoxia-adapted and air control rats. AVP, administered intravenously as bolus injections or sustained infusions, produced major dose-dependent V1-receptor-mediated reductions in mean pulmonary arterial pressure in hypoxia-adapted rats. These effects were comparable in pentobarbital-anesthetized, thoracotomized animals and in conscious, intact rats. Chronic infusions of AVP induced a sustained reduction in mean pulmonary arterial pressure and partially prevented the development of pulmonary hypertension without changing systemic arterial pressure. AVP induced significant decreases in cardiac output in both groups; the cardiac output response was not significantly different in hypoxia-adapted and air control animals. AVP induced almost no change in MPAP in air control rats. Furthermore the systemic pressor effects of AVP were significantly blunted in hypoxia-adapted rats compared with air controls. We conclude that the pulmonary depressor and blunted systemic pressor effects of AVP observed in hypoxia-adapted rats may be related to release of a vasodilator, such as endothelium-derived relaxing factor, vasodilator prostaglandins, or atrial natriuretic peptides. Further study is needed to elucidate these mechanisms and assess the usefulness of AVP and/or its analogues in the treatment and prevention of hypoxia-induced pulmonary hypertension.

Adaptation, Physiological↗
PubMed1989

Dietary Ca2+ supplementation prevents the exaggerated responsiveness of anterior hypothalamic alpha 2-adrenoceptors in NaCl-loaded spontaneously hypertensive rats.

Our previous studies demonstrated that (a) dietary Ca2+ supplementation prevents the rise in blood pressure, activation of sympathetic outflow, and reductions in anterior hypothalamic norepinephrine (NE) content and release induced in NaCl-sensitive spontaneous hypertensive rats (SHR-S) by dietary NaCl loading; and (b) stimulation of alpha 2-adrenoceptors by microinjection of clonidine into the anterior hypothalamic area (AHA) results in an exaggerated depressor response in SHR-S fed a high NaCl diet as compared with SHR-S on a basal diet. The current study tested the hypothesis that dietary Ca2+ supplementation prevents these NaCl induced defects in AHA noradrenergic neurons. SHR-S were placed on diets containing: (a) high NaCl; (b) high Ca2+; (c) high Ca2+, high NaCl; or (d) basal NaCl, basal Ca2+ (control). Two weeks later, clonidine (0.6, 1.2, or 2.5 micrograms) was microinjected into the AHA of conscious rats. Clonidine caused dose-dependent decreases in mean arterial pressure (MAP) and heart rate (HR) that were greater in SHR-S on the high NaCl diet than on the control diet. Ca2+ supplementation prevented the exaggerated depressor response to clonidine in high NaCl-fed SHR-S, but did not reduce the response in SHR-S on the basal NaCl diet. Ca2+ supplementation had no effect on blood pressure (BP) or HR responses to clonidine in control NaCl-resistant SHR (SHR-R) or in normotensive Wistar Kyoto (WKY) rats.

Animals↗
PubMed1989

Dietary Ca2+ prevents NaCl-induced exacerbation of hypertension and increases hypothalamic norepinephrine turnover in spontaneously hypertensive rats.

Dietary calcium (Ca2+) supplementation lowers blood pressure in many forms of genetically mediated and experimentally induced hypertension. The present study tested the hypothesis that neuronal mechanisms underlie the blood pressure-lowering effect of dietary Ca2+ in NaCl-sensitive spontaneously hypertensive rats (SHR-S). SHR-S were fed one of the following diets: control (0.75% NaCl/0.68% Ca2+); high NaCl (8.00% NaCl/0.68% Ca2+); high Ca2+ (0.75% NaCl/2.00% Ca2+), and high NaCl/high Ca2+ (8.00% NaCl/2.00% Ca2+). SHR-S on the 8% NaCl diet for 2 weeks displayed significantly elevated blood pressure (161 +/- 4 mmHg) compared with those on the control diet (139 +/- 3 mmHg). Ca2+ supplementation prevented a rise in blood pressure in rats on the high-NaCl diet but did not alter blood pressure in rats consuming 0.75% NaCl. Plasma norepinephrine stores and turnover in the hypothalamus (anterior and posterior regions), brainstem (pons and medulla) and thoracic spinal cord were assessed using the dopamine-beta-hydroxylase inhibitor 1-cyclohexyl-2-mercapto-imidazole. The 8% NaCl diets reduced anterior hypothalamic region norepinephrine stores and turnover. Concomitant Ca2+ supplementation restored norepinephrine turnover to normal, but did not alter norepinephrine stores in the anterior hypothalamic region. In other regions, no significant differences in norepinephrine content or turnover were observed among groups. In SHR that are resistant to high-NaCl diets (SHR-R), the diets did not alter blood pressure, and neither dietary NaCl nor Ca2+ supplementation affected norepinephrine turnover in any brain region studied. These data indicate that in SHR-S on a diet high in NaCl, Ca2+ supplementation may prevent the NaCl-induced exacerbation of hypertension by increasing norepinephrine turnover in the hypothalamus.

Administration, Oral↗
PubMed1988

The neural basis of salt sensitivity in the rat: altered hypothalamic function.

Dietary NaCl supplementation in NaCl-sensitive spontaneously hypertensive rats (SHR-S) elevates blood pressure, increases peripheral sympathetic nervous system activity and depresses endogenous noradrenaline stores and noradrenaline release in the anterior hypothalamus. NaCl-resistant spontaneously hypertensive rats (SHR-R) and normotensive Wistar Kyoto (WKY) rats are resistant to the NaCl-induced alterations in blood pressure and central and peripheral noradrenergic activity, suggesting that the alterations observed in the SHR-S during NaCl loading are genetically mediated. The anterior hypothalamus is a major cardiovascular regulatory region, and depressor responses elicited by pharmacologic (alpha 2 adrenoceptor) stimulation of this area are exaggerated in SHR-S fed a high NaCl diet compared with SHR-S fed a basal diet and compared with SHR-R and WKY fed a high or basal NaCl diet. Membrane-binding techniques confirm that alpha 2 adrenoceptors in the anterior hypothalamic area are increased in number in SHR-S fed a high NaCl diet, presumably reflecting upregulation in response to reduced local noradrenaline release. These findings are consistent with the hypothesis that decreased noradrenergic activity of sympathoinhibitory neurons in the anterior hypothalamic area may mediate the exacerbation in hypertension that occurs in SHR-S during dietary NaCl supplementation.

Animals↗
PubMed1988

Atrial natriuretic peptide lowers pulmonary arterial pressure in hypoxia-adapted rats.

To test the hypothesis that atrial natriuretic peptide (ANP) has a direct vasodilator effect on the pulmonary vasculature that is enhanced in hypoxia-induced pulmonary hypertension in the rat, we determined the effects of ANP on mean pulmonary (MPAP) and systemic arterial pressure (MSAP) in intact conscious Sprague-Dawley rats exposed to 10% O2 or room air for 4 wk. Catheters were placed in the pulmonary artery through the right jugular vein by means of a closed-chest technique. MPAP and MSAP were monitored before and after intravenous injections of graded doses of ANP. ANP produced dose-related decreases in MPAP that were greater in the hypoxic group than in air controls. There were no significant between-group differences in the systemic depressor responses to ANP or in the ANP-induced reduction in cardiac output. ANP lowered MPAP significantly in isolated perfused lungs from both hypoxia-adapted and air control rats, and this effect was significantly greater in the hypoxic than the air control lungs. These data indicate that ANP lowers pulmonary arterial pressure in rats with hypoxia-induced pulmonary hypertension, mainly by a direct vasodilator effect on the pulmonary vasculature.

Animals↗
PubMed1988

Impaired release of atrial natriuretic factor in NaCl-loaded spontaneously hypertensive rats.

Our previous studies demonstrated that NaCl-sensitive spontaneously hypertensive rats (SHR) of the Okamoto strain exhibit increased blood pressure and reduced noradrenergic input to the anterior hypothalamus area when fed high NaCl diets. The current study tested the hypotheses that 1) release of atrial natriuretic factor (ANF) into the plasma is impaired in NaCl-loaded SHR, a defect that would tend to elevate blood pressure, and 2) ANF levels in regions of brain involved in blood pressure regulation, such as the anterior hypothalamic area, are altered in SHR. SHR and control Wistar-Kyoto rats (WKY) were placed on 1% or 8% NaCl diets at age 7 weeks; 2 weeks later, ANF levels were measured in plasma, left and right atria, anterior hypothalamic area, ventral hypothalamic area, posterior hypothalamic area, pons, and medulla by radioimmunoassay. Blood for ANF assay was obtained from intra-arterial cannulas in conscious, unrestrained rats studied in the resting state. The 8% NaCl diet produced an increase in blood pressure in the SHR, but not in the WKY. Plasma ANF levels were significantly greater in WKY fed 8% NaCl than in WKY fed 1% NaCl, but dietary NaCl loading did not produce similar increases in plasma ANF in the SHR. Plasma ANF levels were not significantly different between SHR and WKY fed the 1% NaCl diet. The observation that dietary NaCl loading stimulated ANF release into the plasma in WKY but not in SHR suggests that the exacerbation in hypertension seen in NaCl-loaded SHR may be related to an impairment in ANF release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Genetic basis of NaCl-sensitive hypertension.

Sensitivity to the pressor effects of dietary NaCl and the depressor effects of dietary Ca2+ is inherited. High NaCl diets accelerate the development and/or exacerbate the severity of hypertension in NaCl-sensitive substrains of spontaneously hypertensive rat (SHR-S) but not in NaCl-resistant substrains of SHR (SHR-R) or in normotensive Wistar-Kyoto (WKY) control rats. High NaCl intake leads to increased circulating noradenaline levels and increased depressor responses to ganglionic blockade in SHR-S but not in SHR-R or WKY rats, indicating that peripheral sympathetic nervous system activity and neurogenic peripheral vascular tone are increased by NaCl supplementation in SHR-S, but not in SHR-R or WKY rats. Further, dietary NaCl loading in SHR-S decreases endogenous noradrenaline stores and noradrenaline release in the anterior hypothalamus, a brain region that contains neurons that give rise to depressor responses when stimulated chemically or electrically. These findings are consistent with the hypothesis that decreased activity of noradrenergic depressor neurons in the anterior hypothalamus may mediate and increase in blood pressure that occurs in NaCl-sensitive animals during dietary NaCl supplementation by releasing tonic inhibition of sympathetic outflow. The exacerbation of hypertension and changes in central noradrenergic activity are observed only in NaCl-loaded SHR-S, not in SHR-R or WKY rats, indicating that these NaCl-induced alterations in central noradrenergic activity are genetically mediated. Dietary Ca2+ supplementation prevents (or reverses) the NaCl-induced changes in blood pressure, peripheral sympathetic nervous system activity, and anterior hypothalamic noradrenaline release in SHR-S, suggesting that dietary NaCl and Ca2+ may have opposing effects on the same regulatory pathway(s). The genetic defect in NaCl/Ca2+ sensitivity of blood pressure is not yet identified, but probably involves cation transport at the cellular level.

Animals↗
PubMed1988

Hypothalamic microinjection of alpha 2-adrenoceptor agonists causes greater sympathoinhibition in spontaneously hypertensive rats on high NaCl diets.

We tested the hypothesis that in NaCl-sensitive spontaneously hypertensive rats (SHR-S) maintained on high NaCl diets, sympathoinhibitory neurons in the anterior hypothalamic area display increased responsiveness to alpha 2-adrenergic receptor stimulation, giving rise to exaggerated depressor responses. Clonidine (0.6-2.5 micrograms) was microinjected directly into the anterior hypothalamic area of SHR-S maintained for 2 weeks on high (8%) and normal (1%) NaCl diets, and blood pressure and heart rate responses were monitored. Controls were NaCl-resistant SHR (SHR-R) and normotensive Wistar-Kyoto (WKY) rats. Clonidine microinjection into the anterior hypothalamic area resulted in dose-dependent rapid-onset depressor and bradycardic responses that were significantly greater in SHR-S fed on a high NaCl diet. In SHR-R and WKY rats, the high NaCl diet had no significant effect on blood pressure or heart rate responses to clonidine. Further studies demonstrated that the response to microinjection of clonidine into the rat anterior hypothalamic area was location-specific, since injections into surrounding hypothalamic nuclei gave a longer latency in the onset of either depressor and bradycardic responses or pressor and tachycardic responses. The response of clonidine was blocked by concurrent microinjection of the selective alpha 2-adrenergic antagonist rauwolscine but not by the alpha 1-adrenergic antagonist prazosin, confirming that the response was alpha 2-adrenoceptor-specific. Microinjection of the selective alpha 2-agonist guanabenz into the anterior hypothalamic area produced depressor and bradycardic responses in SHR-S and Sprague-Dawley rats, while microinjection of the selective alpha 1-agonist phenylephrine into the anterior hypothalamic area had no effect on either blood pressure or heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Blunted pressor responsiveness to quinpirole, a specific dopamine D2 receptor agonist, in conscious deoxycorticosterone acetate/NaCl hypertensive rats is related to atrial natriuretic peptide release.

Our previous studies have demonstrated: 1) that i.v. quinpirole (LY171555), a selective dopamine D2 receptor agonist, has a dose-dependent pressor effect in conscious rats which is mediated by activation of sympathetic outflow and vasopressinergic activity, and 2) that the activity of central dopaminergic neurons is reduced in deoxycorticosterone acetate (DOCA)/NaCl hypertensive rats. To elucidate the role of central and peripheral dopaminergic systems in the pathogenesis of DOCA/NaCl hypertension, we examined the effects of quinpirole on mean arterial pressure, heart rate, plasma norepinephrine, epinephrine, arginine vasopressin and atrial natriuretic peptide (ANP) in conscious 4-week-old DOCA/NaCl hypertensive and normotensive control rats. Quinpirole (1 mg/kg i.v.) increased mean arterial pressure in both groups, but the pressor response was attenuated in DOCA/NaCl rats. Paradoxically, quinpirole-induced increments in plasma norepinephrine, epinephrine and arginine vasopressin were greater in DOCA/NaCl rats. In addition, quinpirole induced a 2-fold increase in plasma ANP (P less than .01) in both DOCA/NaCl and control rats. Pretreatment with domperidone (2.5 mg/kg i.v.), a peripherally acting dopamine D2 antagonist, enhanced the maximum pressor response to quinpirole in both groups, restored the quinpirole-induced pressor response to control levels in the DOCA/NaCl rats and blocked the stimulatory effect of quinpirole on ANP release in both groups. These data indicate that peripheral dopamine D2 receptors modulate ANP secretion in the rat. The observation that the quinpirole-induced increment in plasma ANP was enhanced in DOCA/NaCl rats supports the hypothesis that the blunted pressor response to quinpirole in this model is related to enhanced ANP release.

Animals↗
PubMed1987

Altered responsiveness of regional brain dopamine and DOPAC levels to systemic administration of quinpirole, a dopamine D2 agonist, in DOCA/NaCl-hypertensive rats.

Our previous studies have demonstrated that administration of quinpirole (LY171555), a potent and highly selective dopamine (DA) D2 receptor agonist, to conscious Sprague-Dawley rats produces increases in arterial pressure through the activation of sympathetic outflow and vasopressinergic activity. To test the hypotheses that quinpirole inhibits in vivo release of DA from central dopaminergic neurons by activation of DA receptors in the central nervous system (CNS) and that this mechanism may be altered in the desoxycorticosterone acetate (DOCA)/NaCl model of hypertension, we examined the effects of quinpirole on stores of DA and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in brain regions of 4-week DOCA/NaCl-hypertensive rats and their normotensive controls. Levels of DA and DOPAC were measured in brain regions by HPLC 15 min after the i.v. administration of quinpirole (1 mg/kg). Quinpirole resulted in a significant increase in DA stores and decrease in DOPAC stores in most brain regions examined in both DOCA/NaCl-hypertensive rats and normotensive controls, presumably by inhibiting DA release through a presynaptic mechanism. In the vehicle-treated groups, DA stores in the anterior hypothalamus and DOPAC stores in the nucleus accumbens were lower in DOCA/NaCl-hypertensive rats than in H2O controls. Following quinpirole administration, DA stores in the anterior hypothalamus increased significantly in DOCA/NaCl-treated rats but not in H2O controls and DOPAC stores in the nucleus accumbens decreased significantly in H2O control rats but not in DOCA/NaCl-treated rats. These observations provide further evidence for the presence of inhibitory DA D2 receptors which modulate the activity of dopaminergic neurons in the CNS.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Blunted responsiveness of posterior hypothalamic norepinephrine to quinpirole in DOCA/NaCl hypertensive rats.

Our previous studies have demonstrated that the specific dopamine D2 receptor agonist, quinpirole (LY171555), has a pressor effect in conscious normotensive rats and that this is accompanied by a centrally mediated increase in sympathetic activity and arginine vasopressin release. This pressor response to quinpirole is blunted in the DOCA/NaCl hypertensive rat. To examine the hypothesis that the responsiveness of the central noradrenergic and serotonergic systems to quinpirole treatment is altered in DOCA/NaCl rats, the norepinephrine (NE), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) contents of hypothalamic and brainstem areas were measured in 4-week DOCA/NaCl hypertensive and H2O control rats 15 minutes after the intravenous administration of quinpirole (1 mg/kg). The results demonstrate that quinpirole selectively reduced (26%) posterior hypothalamic NE content in control rats, but not in DOCA/NaCl hypertensive rats. The NE content in the spinal cord and 5-HIAA content in the pons were greater in DOCA/NaCl rats than in normotensive controls in both saline and quinpirole treated groups. Our data suggest that the specific D2 agonist may effect its central pressor response by stimulating NE release from posterior hypothalamic area, a "pressor" region of hypothalamus, and that this D2 agonist induced pressor mechanism may be blunted in DOCA/NaCl hypertension.

Animals↗