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T Unger

Publications and source records attributed to T Unger.

At least 289 records · Page 16Linked to original sources
PubMed1986

The central pressor actions of substance P are inhibited by GABA.

The influence of GABA-ergic stimulation on the centrally evoked pressor and tachycardic responses to substance P (SP) was investigated in conscious rats. Intracerebroventricular (i.c.v.) pretreatment with the potent GABA agonist muscimol attenuated the pressor responses to i.c.v. administered SP in a dose-dependent and reversible fashion. Inhibition was maximal 5-60 min after muscimol injection and lasted up to 3 h. In contrast, the increases in heart rate in response to i.c.v. administered SP were not consistently inhibited by muscimol. Central pretreatment with muscimol prevented the increase of plasma adrenaline but not of plasma noradrenaline in response to i.c.v. administered SP. Our results demonstrate that the GABA-ergic system can exert an inhibitory control on pathways mediating the central pressor actions of SP. The selective inhibition of adrenaline secretion by muscimol implies that suppression of sympathetic outflow to the adrenal gland may be involved as an important mechanism. In addition, our findings point to a dissociation between pathways mediating the pressor and tachycardic effects of SP.

Animals↗
PubMed1986

The phorbol ester induced atrial natriuretic peptide secretion is stimulated by forskolin and Bay K8644 and inhibited by 8-bromo-cyclic GMP.

The role of intracellular signals in the regulation of atrial natriuretic peptide (ANP) release was studied using the isolated perfused rat heart. The phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), known to activate the protein kinase C pathway, produced a dose-dependent increase in perfusate ANP immunoreactivity. Bay k8644, a putative calcium channel activator, and forskolin, which stimulates adenylate cyclase, induced a sustained increase in ANP secretory rate. TPA in combination with either Bay k8644 or forskolin induced higher ANP secretion than the calculated additive value for each agent. 8-bromo-cyclic GMP and sodium nitroprusside, when given alone, had no effect on ANP secretion, but delayed the TPA-stimulated increase in perfusate ANP. ANP secretion appears therefore to be mediated both by the phosphoinositide and the cAMP system, whereas the cGMP pathway may be inhibitory.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Baroreceptor reflex effect on sympathetic nerve activity in stroke-prone spontaneously hypertensive rats.

To elucidate the relationship between responses in sympathetic outflow to incremental changes in blood pressure, we performed baroreflex activation experiments in conscious, stroke-prone, spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. We gave incremental bolus injections of nitroprusside and methoxamine and measured mean blood pressure (MAP), heart rate, and splanchnic nerve activity (SpNA). Change in heart rate per change in blood pressure was greater in WKY rats than in SHRSP indicating the decrease in baroreceptor sensitivity displayed in the latter strain. In contrast, change in SpNA per change in blood pressure was greater in SHRSP than in WKY rats. These findings suggest that sympathetic outflow in SHRSP is more reactive to blood pressure changes than in WKY rats. The discordance in heart rate and SpNA changes supports the notion that central neural integration of autonomic function in SHRSP is impaired.

Animals↗
PubMed1986

Atrial natriuretic factor determinations and chronic sodium homeostasis.

To examine the physiological role of atrial natriuretic factor (ANF) in the maintenance of sodium homeostasis under various conditions, we performed experiments in rats across a wide range of sodium intake, in rats with chronic renal insufficiency at extremes of sodium intake, and in rats given desoxycorticosterone acetate. After three weeks of a very low sodium diet, regular diet, or regular diet plus 1% saline as drinking water, no difference in plasma values of immunoreactive atrial natriuretic factor (IR-ANF) were identified, while rats at the lowest level of sodium intake had elevated atrial values. Normal rats, and rats with 5/6 nephrectomy has plasma values of IR-ANF which were no different irrespective of their sodium intake, nor were atrial values in these rats different. Although mineralocorticoid "escape" could be documented by changes in urine sodium excretion, neither plasma nor atrial IR-ANF values showed differences either at 24 or 72 hr after "escape". The data are consistent with previous observations that ANF serves the purpose of affecting rapid adjustments to large alterations in circulating fluid volume. Chronic high sodium intake, adaptation to renal insufficiency, and adjustment to the effect of mineralocorticoid do not appear to be associated with increased circulating plasma concentrations of IR-ANF.

Animals↗
PubMed1986

Differential actions of neuronal and hormonal vasopressin on blood pressure and baroreceptor reflex sensitivity in rats.

The central cardiovascular actions of arginine vasopressin (AVP) and the role of this peptide in the modulation of baroreceptor reflex (BRR) sensitivity were investigated in conscious, chronically instrumented rats. Intracerebroventricular (i.c.v.) injections of AVP (1-100 ng) produced dose-dependent pressor effects together with increases in heart rate, splanchnic, and renal sympathetic nerve activity and a reduction of mesenteric blood flow. These responses were prevented by i.c.v. pretreatment with a V1-AVP receptor antagonist. Furthermore, the central pressor effects of AVP were abolished by peripheral alpha-adrenoceptor blockade with phentolamine. In contrast to the i.c.v. injections, intravenous (i.v.) or intracarotid injections of AVP produced pressor responses accompanied by bradycardia and a decrease in sympathetic nerve activity. Intracerebroventricular pretreatment with a V1-AVP receptor antagonist shifted the slope of the BRR curve (increases in pulse interval plotted against increases in systolic blood pressure in response to i.v. methoxamine) toward higher sensitivity, whereas i.v. pretreatment with a V2-AVP receptor antagonist shifted the slope of the BRR curve toward lower sensitivity of the reflex. These findings suggest that central (neuronal) AVP, by acting on V1-AVP receptors in the brain, participates in central pressor mechanisms, activates the sympathetic nervous system, and desensitizes the BRR. Conversely, circulating (hormonal) AVP can sensitize the BRR by acting on V2-AVP receptors accessible from the blood. Our data provide evidence pointing to a direct interaction between the neuronal and the hormonal axis of the AVP system within cardiovascular control.

Animals↗
PubMed1986

Tissue converting enzyme and cardiovascular actions of converting enzyme inhibitors.

The discovery of tissue renin-angiotensin systems (RAS) in organs controlling the cardiovascular system has opened new perspectives for our understanding of the cardiovascular actions of converting enzyme (CE) inhibitors. Direct application of CE inhibitors to the brain and heart entails distinct cardiovascular effects. Systemic treatment with CE inhibitors leads not only to an inhibition of the plasma RAS, but it also inhibits tissue CE in various organs and reduces local angiotensin II concentrations. Evidence is presented that oral CE inhibitor treatment markedly influences organ function of the heart, brain, and vascular wall independently of the plasma RAS. These findings are compatible with the concept that tissue CE inhibition contributes to the beneficial actions of CE inhibitors in cardiovascular disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Effect of urapidil, clonidine, and prazosin on sympathetic tone in conscious rats.

To test the hypothesis that the hypotensive action of urapidil is in part related to a direct action on the brain, the central (intracerebroventricular) and peripheral (intravenous) effects of urapidil were studied and compared with those obtained with clonidine and prazosin. All studies were conducted in conscious, chronically instrumented stroke-prone spontaneously hypertensive rats (SHRSP). Efferent sympathetic nervous system activity was estimated by means of a bipolar electrode implanted on the splanchnic nerve. Only clonidine, administered intracerebroventricularly and intravenously, decreased sympathetic nerve activity. Urapidil and prazosin either did not affect sympathetic nerve activity after central administration or increased it after peripheral administration at low and high doses, respectively. Centrally administered urapidil and prazosin lowered blood pressure but also blocked the response to intravenously administered phenylephrine; this result suggests a peripheral effect. Centrally administered urapidil decreased heart rate. Urapidil given either intracerebroventricularly or into the cisterna magna had no influence on baroreceptor responses. Intravenous infusions of urapidil and prazosin in sufficient doses to lower blood pressure in spontaneously hypertensive rats by 50 mm Hg completely blocked the actions of phenylephrine. These data suggest that in conscious SHRSP urapidil lowers blood pressure through peripheral blockade of alpha 1-adrenergic receptors rather than by means of central sympathetic suppression. In this regard urapidil resembles prazosin rather than clonidine; however, the effect of urapidil on heart rate is consistent with a central mode of action.

Animals↗
PubMed1986

Differential modulation of the baroreceptor reflex by brain and plasma vasopressin.

Plasma vasopressin sensitizes the baroreceptor reflex, whereas vasopressin given into the cerebral ventricle overrides the baroreceptor reflex by means of sympathetic stimulation. To test the hypothesis that arginine vasopressin stimulates two different receptor subtypes (V1 and V2) in the central nervous system, we measured the baroreceptor reflex (change in pulse interval vs change in blood pressure) after administering methoxamine (10-300 micrograms/kg i.v.) in conscious rats. Animals were pretreated either with a V1 vasopressin receptor antagonist administered intravenously or intracerebroventricularly, or with a V2 receptor antagonist administered intravenously. The central V1 antagonist caused sensitization of the baroreceptor reflex, whereas the intravenous V2 antagonist attenuated it. The intravenous V1 vasopressin antagonist had no effect on baroreceptor reflex sensitivity. When the experiments were repeated in rats with hereditary diabetes insipidus, neither antagonist influenced the baroreceptor reflex. Volume expansion lowered circulating vasopressin levels and also attenuated the baroreceptor reflex--effects similar to those observed with the intravenous V2 antagonist. We conclude that vasopressin sensitizes the baroreceptor reflex through V2 receptors accessible from the blood and inhibits the reflex through V1 receptors in the brain that cannot be reached from the blood. These observations suggest a direct interaction between hormonal and neuronal vasopressin in cardiovascular control.

Animals↗
PubMed1986

Atriopeptin III kinetics and pharmacodynamics in normal and anephric rats.

To elucidate the disposition of atriopeptin III in plasma we performed experiments in normal and anephric rats. Bolus, i.v. atriopeptin III (250 ng) was given after which the rats were decapitated at 30-sec intervals. The half-life of atriopeptin III in normal rats was 26.5 sec, the volume of distribution was 352 ml and the plasma clearance was 500 ml/min. In anephric rats the half-life was 56.8 sec, the volume of distribution was 345 ml and the plasma clearance was 206 ml/min. In other rats atriopeptin III was given and urine was collected simultaneously. No atriopeptin III could be measured in the urine. We gave 0.0, 0.067, 0.125, 0.25, 0.5 and 1.0 ng/kg of bolus atriopeptin III to normal rats and measured effects on blood pressure, heart rate and plasma concentration at 30 sec, the time at which maximum effect on blood pressure occurred. Dose, change in blood pressure and plasma concentration were correlated. Heart rate increased, but not in a dose-dependent fashion. We conclude that atriopeptin III is cleared from rat plasma rapidly and that the kidneys account for 59% of its elimination by degradation rather than excretion. Because the effect of atriopeptin III on blood pressure is concentration-dependent, the transient changes exerted by atriopeptin III may be related to its rapid disappearance from plasma.

Animals↗
PubMed1986

Plasma atrial natriuretic peptide values in cardiac disease.

The plasma concentrations of atrial natriuretic peptides (ANP) were measured during cardiac catheterization in 137 patients with heart disease. Atrial natriuretic peptides were elevated in all types of cardiac disease investigated, including valve disease, coronary heart disease and cardiomyopathy. The highest plasma ANP concentrations were found in patients with the most marked impairment of ventricular function and mitral valve disease. In patients with coronary heart disease, a significant, direct linear correlation was found between left ventricular filling pressure and plasma ANP concentrations (r = 0.42, P less than 0.001). Similarly, in patients with cardiomyopathy, a linear relationship was found between mean pulmonary artery pressure and plasma ANP concentration (r = 0.80, P less than 0.01). These observations suggest that measurement of ANP may be of value as a non-invasive humoral marker in the diagnosis of various cardiac diseases.

Atrial Natriuretic Factor↗
PubMed1986

Antihypertensive action and inhibition of tissue converting enzyme (CE) by three prodrug CE inhibitors, enalapril, ramipril and perindopril in stroke-prone spontaneously hypertensive rats.

The active diacids of the new converting enzyme (CE) inhibitors ramipril and perindopril proved to possess a similar inhibitory potency against rat plasma CE in vitro. Both diacids were more active than enalaprilic acid or captopril. In stroke-prone spontaneously hypertensive rats (SHRSP) chronic oral treatment for 2 weeks with enalapril (30 mg/kg per day), ramipril or perindopril (each 1 mg/kg normalized blood pressure. The CE inhibitor-induced changes in parameters of the plasma renin-angiotensin system [angiotensin I (ANG I), angiotensin II (ANG II), PRC and CE activity] followed the expected pattern, but were not quantitatively related to the antihypertensive action of the three CE inhibitors. Four weeks of oral equi-dose treatment with the three CE inhibitors (10 mg/kg per day) inhibited tissue CE activity in various organs including kidney, heart, vascular wall and brain. Ramipril and perindopril lowered blood pressure and tissue CE activity more potently than enalapril did. These results are consistent with the hypothesis that CE inhibition in tissue with subsequent local reduction of ANG II synthesis may contribute to the antihypertensive mechanisms of CE inhibitors.

Angiotensin II↗
PubMed1986

[Antihypertensive action and inhibition of tissue conversion enzyme by ramipril, perindopril and enalapril in the spontaneously hypertensive rat (SHRSP)].

Ramipril and perindopril, the active diacids of two new converting enzyme (CE) inhibitors proved to possess a similar inhibitory potency against rat plasma CE in vitro. These diacid compounds were more active than enalaprilic acid or captopril. In stroke-prone spontaneously hypertensive rats (SHRSP) chronic oral treatment for two weeks with enalapril (30 mg/kg per day), ramipril or perindopril (each 1 mg/kg per day) normalized blood pressure. The CE inhibitor-induced changes in parameters of the plasma renin-angiotensin system (angiotensin I, angiotensin II, PRC, CE activity) followed the expected pattern, but were not quantitatively related to the antihypertensive action of the three inhibitors. Four weeks of oral equi-dose treatment with the three CE inhibitors (10 mg/kg per day) inhibited tissue CE activity in various organs including kidney, heart, vascular wall and brain. Ramipril and perindopril lowered blood pressure and tissue CE activity more potently than enalapril. These results confirm the hypothesis that CE inhibition in tissue with subsequent local reduction of ANG II synthesis may contribute to the antihypertensive mechanisms of CE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Influence of beta-aminopropionitril on media hypertrophy and baroreceptor reflex in normotensive and hypertensive rats.

Experiments were performed to investigate the antihypertensive action of beta-aminopropionitril (BAPN) in normotensive and hypertensive rats and to elucidate the role of media hypertrophy and arterial wall distensibility on baroreceptor reflex and blood pressure (BP) regulation. Normotensive Wistar-Kyoto rats (WKY), DOCA-salt hypertensive WKY, and stroke-prone spontaneously hypertensive rats (SHRSP) were treated with BAPN (100 mg/kg per day, intraperitoneally) for 10 weeks. The respective control groups (n = 10 per group) received 0.9% NaC1 instead of BAPN. In BAPN-treated groups the BP of DOCA-salt WKY (145 versus 170 mmHg) and SHRSP (170 versus 208 mmHg) was lower than that of controls at the end of the treatment period. In BAPN-treated rats, the medial cross-sectional area was reduced, postmortem distensibility of vascular wall was greater, and baroreceptor reflex, estimated from heart rate responses to BP changes, showed steeper regression curves. The BAPN-induced BP decrease in the hypertensive rats demonstrates that the level of sensitivity of the baroreceptor reflex is related to the mechanical properties of the arterial wall.

Aminopropionitrile↗
PubMed1985

Effects of converting enzyme inhibitors: ramipril and enalapril on peptide action and sympathetic neurotransmission in the isolated heart.

The role of converting enzyme (CE) in heart function was studied by assessing the inhibition of CE activity in rat heart tissue and in isolated perfused hearts from rat, guinea-pig and rabbit (Langendorff technique). Angiotensin I (ANG I) added to the perfusate reduced coronary flow (FLO) in all species, increased force of contraction (CON) in rats, decreased CON in guinea-pigs and had no effect on CON in rabbits. In contrast, bradykinin (BK) increased FLO in all species, decreased CON in rats, increased CON in guinea-pigs and had no effect on CON in rabbits. The CE inhibitors ramipril (HOE498) 1 mg/kg and enalapril (MK421) 30 mg/kg given orally 1 h prior to killing of the animals inhibited the ANG I effects and potentiated the BK effects but had no effects on the action of ANG II. The same doses of the two CE inhibitors produced up to 24 h inhibition of CE activity measured biochemically in the heart after single oral doses. Electrical sympathetic stimulation of the cardiac nerves (SNS) in isolated rabbit heart resulted in an increase of HR and CON and in an initial decrease and subsequent increase of FLO. The effects of SNS on HR and FLO were significantly reduced following HOE498 (1 mg/kg) pretreatment. The results suggest that local CE is involved in the regulation of peptide effects in the heart, including the ANG II-mediated facilitation of neurotransmission.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

The cardiovascular effects of oxytocin in conscious male rats.

In conscious, chronically instrumented normotensive male Wistar rats intravenous (i.v.) administration of oxytocin (OXT) (greater than or equal to 100 ng) induced a dose-related biphasic change in mean arterial pressure (MAP). This consisted of an initial pressor effect accompanied by bradycardia and a decrease in cardiac output (CO), followed by a more prolonged fall in MAP which reached a maximum 30 min after injection and was accompanied by an increase in CO. The more specific (Thr4,Gly7]OXT analogue (0.01-10 micrograms i.v.) caused a dose-related fall in MAP and a rise in CO which reached a maximum after 15-30 min. Similarly in spontaneously hypertensive rats of the stroke prone strain (SHRSP) an initial pressor effect and delayed fall in MAP were apparent after OXT (0.1 and 10 micrograms i.v.) only the decrease in MAP being evident with the [Thr4,Gly7]OXT analogue. These responses were significantly larger than those observed in Wistar Kyoto controls. The pressor effects are therefore interpreted to be due to vasopressin receptor activation while the depressor effects appear to be oxytocin specific. In sinoaortic denervated rats, OXT (0.1 and 10 micrograms i.v.) induced an enhanced initial pressor effect with a much reduced reflex bradycardia and fall in CO. A larger and more prolonged delayed fall in MAP was apparent with both OXT and [Thr4,Gly7]OXT accompanied by a decrease in CO when compared to sham-operated controls. Intracisternally (i.c.) administered OXT (0.05-10 ng) had no effect on MAP or heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗