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Biomedical subjects

T Unger

Publications and source records attributed to T Unger.

At least 253 records · Page 14Linked to original sources
PubMed1989

Effects of intravenous AVP on cardiac output, mesenteric hemodynamics, and splanchnic nerve activity.

To elucidate the effects of intravenous arginine vasopressin (AVP) on the neural control of the circulation, we investigated the action of AVP on neural circulatory control with respect to its influence on cardiac output (CO), mesenteric blood flow (MBF), and splanchnic nerve activity (SpNA) in conscious rats. We implanted Doppler flow probes and bipolar electrodes into seven Wistar rats for continuous monitoring of CO, MBF, and SpNa. After the infusion of four different equipressor doses of AVP and methoxamine, the decreases in heart rate (HR) and CO were significantly greater with AVP than with methoxamine. Pretreatment with atenolol and methscopolamine bromide abolished the decreases in HR after both AVP and methoxamine injections but attenuated the AVP-induced decreases in CO less than the methoxamine-induced CO decreases. In untreated rats and in rats receiving cardiac autonomic blockade, the reduction in MBF and the increases in mesenteric resistance were greater after AVP than after methoxamine. Furthermore, SpNA decreased to a greater extent with all doses of AVP than with methoxamine. We conclude that in the rat the exaggerated reduction in CO induced by circulating AVP is not because of a sensitization of neural mechanisms but rather to caridac actions of the peptide. In contrast, AVP sensitizes the sympathetic control of the mesenteric vascular bed to counterbalance its potent local vasoconstrictor effects.

Animals↗
PubMed1989

Central effects of somatostatin: pressor response, AVP release, and sympathoinhibition.

The effects of intracerebroventricular (icv) administration of somatostatin(1-14) (SS1-14) on mean arterial blood pressure (MAP), heart rate (HR), plasma arginine vasopressin (AVP) concentration, and splanchnic nerve activity (SpNA) were studied in conscious rats. In addition, the effects of peripheral alpha-adrenergic receptor blockade with prazosin, vasopressinergic V1-receptor blockade with [d(CH2)5Tyr(Me)]AVP, and chronic bilateral sinoaortic denervation (SAD) on central SS1-14-induced MAP, HR, and SpNA responses were investigated. SS1-14 icv elicited dose-dependent increases in MAP and plasma AVP concentration as well as decreases in HR and SpNA. Prazosin iv did not significantly affect SS1-14-induced pressor and bradycardic responses but augmented the decrease in SpNA. The V1-AVP receptor antagonist iv significantly attenuated the effects of SS1-14 icv on MAP, HR, and SpNA. Following SAD the pressor responses to SS1-14 icv were significantly enhanced and were associated with significantly smaller decreases in HR and SpNA. We conclude that central administration of SS1-14 causes a pressor response via release of AVP while at the same time inhibiting peripheral sympathetic outflow. Our results support the hypothesis that SS1-14 in the brain by its effects on AVP release and sympathetic outflow may participate in central cardiovascular regulation.

Adrenergic alpha-Antagonists↗
PubMed1989

Hypertension transmitted by kidneys from stroke-prone spontaneously hypertensive rats.

We determined whether transplantations of kidneys from stroke-prone spontaneously hypertensive rats (SPSHR) and from normotensive Wistar-Kyoto rats (WKY) alter blood pressure in renal graft recipients. Kidneys taken from seven male SPSHR and seven male WKY rats (blood pressure 186 +/- 4.8 and 111 +/- 3.7 mmHg, respectively) at the age of 20 wk were transplanted, using microsurgical techniques, to bilaterally nephrectomized age-matched male F1 hybrids (blood pressure 136 +/- 2.6 and 138 +/- 6.3 mmHg, respectively) bred from SPSHR and WKY parents. After renal transplantation, blood pressure in recipients of SPSHR kidneys rose to 146 +/- 11.8 (week 2), 163 +/- 16.4 (week 3), 192 +/- 17.1 (week 4), 222 +/- 17.7 (week 5), 221 +/- 12.6 (week 6), 218 +/- 20.3 (week 7), and 239 +/- 9.2 mmHg (week 8). There was no significant change in blood pressure in recipients of WKY kidneys. All rats recovered rapidly from surgery. After renal transplantation, there was a significant increase in daily water intake, a decrease in plasma renin activity, and a slight rise in plasma urea concentration. Our data show that transplantation of kidneys from adult SPSHR causes hypertension in normotensive recipients, indicating a major function for the kidney in SPSHR hypertension.

Animals↗
PubMed1989

Angiotensin-induced hypertension in the rat. Sympathetic nerve activity and prostaglandins.

To elucidate mechanisms of angiotensin II (Ang II)-related hypertension, we infused angiotensin (76 ng/min s.c.) into rats with minipumps for 10-14 days. Control rats received sham pumps. We measured blood pressure by tail-cuff, and the excretion of aldosterone and prostaglandins (PG) (PGE2, prostacyclin derivative 6kPGF1 alpha, and thromboxane [Tx] derivative TxB2). Angiotensin II increased blood pressure by 20 mm Hg by day 2 and by 90 mm Hg by day 10. Aldosterone excretion increased from 10 to 70 ng/day in Ang II rats by day 7. Urine PGE2 did not increase in angiotensin rats; however, both 6kPGF1 alpha and TxB2 excretion increased with angiotensin. Control rats had no changes in any of these parameters. A sympathetic component was tested in a separate group of angiotensin rats that received phenoxybenzamine (300 micrograms/kg/day) during angiotensin infusion; their increase in blood pressure of 40 mm Hg at 10 days was less than in those rats with angiotensin alone but more than in control rats. Phenoxybenzamine did not influence the angiotensin-induced increases in excretion of 6kPGF1 alpha or TxB2. Additional groups of conscious angiotensin and control rats were equipped with splanchnic nerve electrodes on day 14 for recording of sympathetic nerve activity. Angiotensin rats had greater basal sympathetic nerve activity than the control rats. Incremental methoxamine injections demonstrated altered baroreceptor reflex function in rats receiving angiotensin. We conclude that increased blood pressure with chronic angiotensin infusion is accompanied by increased production of aldosterone and increased sympathetic tone. The latter may be modulated by PG.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Inhibition of converting enzyme in brain tissue and cerebrospinal fluid of rats following chronic oral treatment with the converting enzyme inhibitors ramipril and Hoe 288.

A direct central nervous system (CNS)-related component of the cardiovascular actions of converting enzyme (CE) inhibitors will be governed by the ability of these drugs to gain access to the brain. We investigated the inhibitory effect of the two CE inhibitors ramipril and Hoe 288 on CE activity in different brain regions and in the cerebrospinal fluid of rats. One-week oral gavage treatment with ramipril (10 mg/kg/day) and Hoe 288 (10 mg/kg/day) resulted in a marked inhibition of CE activity in the brain cortex (90 and 91%, respectively), the hypothalamus (78 and 82%, respectively), and in the brainstem (67 and 66%, respectively). The complete blockade of plasma CE activity was paralleled by a 84% inhibition of CE activity in cerebrospinal fluid. Both CE inhibitors failed significantly to inhibit CE activity in the striatum. Our results demonstrate that the CE inhibitors Hoe 288 and ramipril were able to pass the blood-brain barrier (BBB) to inhibit central CE activity. The penetration of CE inhibitors into the CNS appears to depend on the lipophilicity of the drugs and on the mode of drug application. The possibility that an inhibition of CE activity in circumventricular organs outside the BBB such as the subfornical organ and the organum vasculosum of the lamina terminalis may be sufficient to explain the central effects of orally applied CE inhibitors is discussed.

Administration, Oral↗
PubMed1989

Inhibition of converting enzyme in the cerebrospinal fluid of rats after oral treatment with converting enzyme inhibitors.

Inhibition of brain converting enzyme (CE) has been implicated in the antihypertensive action of some CE inhibitors. However, it is still a matter of debate whether these drugs gain access to the central nervous system upon systemic administration. In this study in rats we investigated the ability of p.o. applied CE inhibitors to penetrate from blood into cerebrospinal fluid (CSF) by analyzing the inhibition of CE activity in the CSF after acute bolus and after 1 week overnight treatment with enalapril, ramipril and Hoe 288. Penetration into the CSF closely paralleled the lipid solubility of the drugs. The most lipophilic drug, Hoe 288 (10 mg/kg), inhibited CE activity in the CSF after acute (66%) and after chronic (30%) p.o. treatment. Ramipril (10 mg/kg), being less lipophilic than Hoe 288, was only effective after acute bolus administration (59% inhibition), whereas the most hydrophilic drug, enalapril (30 mg/kg), did not reduce CE activity in the CSF after either regimen. The CE inhibition in the CSF after acute p.o. treatment with ramipril and Hoe 288 was dose-dependent with threshold doses of 3 to 10 mg/kg (ramipril) and less than 1 mg/kg (Hoe 288). The presence of ramipril and Hoe 288 in the CSF was also demonstrated by the inhibitory effect of heat-inactivated CSF from CE inhibitor-treated rats on purified CE from rabbit lung. A comparison of the in vitro activities of the three prodrugs and their parent diacids against CE in plasma and in CSF and against purified CE revealed hydrolysis of the prodrugs to their parent diacids in plasma and CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Central noradrenergic pathways are not involved in the pressor response to intracerebroventricular substance P.

Intracerebroventricular (i.c.v.) pretreatment of Wistar rats with the catecholaminergic neurotoxin, 6-hydroxydopamine, significantly reduced noradrenaline in the pons/medulla (by 73%) and almost abolished the noradrenaline levels in the spinal cord (by 89%). The pressor response of these animals to i.c.v. angiotensin II (ANGII, 10 ng) was significantly attenuated. In contrast, there was no significant effect on the pressor response to i.c.v. substance P (SP, 100 ng). The results provide evidence that different central pathways mediate the pressor response to ANGII and SP.

Angiotensin II↗
PubMed1988

Endogenous tissue renin-angiotensin systems. From molecular biology to therapy.

Expression of the genes for renin and angiotensinogen has been documented in the heart and brain of several species, including rodents and primates. In the same tissues, local generation of angiotensin II has also been demonstrated. Neuropeptidergic brain angiotensin and local cardiac angiotensin participate in cardiovascular regulation. Inhibition of cardiac angiotensin II protects against deleterious arrythmogenic and metabolic effects of transient regional myocardial ischemia, and blockade of brain angiotensin II effectively lowers blood pressure in spontaneously hypertensive rats. It is surmised therefore that the therapeutic effects of converting enzyme inhibitors are, in part, brought about by inhibition of local tissue angiotensin II generation in addition to their interference with the hormonal plasma renin-angiotensin system. This would help to explain their therapeutic efficacy in pathophysiologic conditions in which hypertension is associated with low plasma renin activity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Renin-dependent water intake in hypovolemia.

The role of the renin-angiotensin system as a mediator of water intake, induced by hypovolemia after polyethylene glycol (PEG) injection, was investigated. Blockade of angiotensin I converting enzyme and of angiotensin receptors was used as a pharmacological tool. A significant reduction of water intake was observed when angiotensin I converting enzyme was inhibited by captopril and enalapril. In PEG-treated rats with blockade of angiotensin I converting enzyme, hypertonic saline injection continued to elicit substantial drinking. Normalization of low blood pressure by vasopressin infusions in PEG and captopril treated rats did not interfere with the antidipsogenic effectiveness of converting enzyme blockade. The angiotensin II receptor antagonist, saralasin, also reduced PEG-induced drinking although less effectively than converting enzyme inhibitors. We conclude that water intake due to isotonic depletion of the extracellular fluid compartment may depend on the activity of the renin-angiotensin system.

Angiotensin II↗
PubMed1988

Effect of sodium chloride and sodium bicarbonate on blood pressure in stroke-prone spontaneously hypertensive rats.

1. To test the hypothesis that NaCl increases blood pressure, while NaHCO3 does not, we measured the effect of an NaHCO3-containing mineral water on blood pressure in stroke-prone spontaneously hypertensive (SHR-SP) and Wistar-Kyoto (WKY) rats. We compared mineral water with equimolar amounts of NaCl and demineralized drinking water in six groups of 20 rats each over 24 weeks. 2. NaCl consistently increased blood pressure in both SHR-SP and WKY compared with demineralized water, while mineral water did not. 3. We studied the possible role of sodium-regulating hormones. Sodium, potassium-dependent adenosine triphosphatase activity was decreased by NaCl and by age, but not by mineral water. The concentration of atrial natriuretic peptide was greater in SHR-SP, but was not influenced by the two regimens. Components of the renin-angiotensin-aldosterone system and 18-hydroxydeoxycorticosterone tended to decrease with NaCl, but not with mineral water. 4. Plasma pH values in the six groups of rats were not different; however, SHR-SP had consistently lower PCO2 and HCO3- values and higher anion gap values than WKY rats. These values were not influence by the two regimens. 5. NaCl elevates blood pressure in SHR-SP while NaHCO3 does not. The changes in hormones regulating sodium homoeostasis suggest that NaCl induces volume expansion while NaHCO3 does not. The effect may be related to influences on renal sodium reabsorption by chloride and bicarbonate. The possible role of increased proton excretory activity in SHR-SP remains to be determined.

Animals↗
PubMed1988

Effect of a prostacyclin derivative (iloprost) on regional blood flow, sympathetic nerve activity, and baroreceptor reflex in the conscious rat.

We have investigated the hemodynamic actions of iloprost, a stable prostacyclin derivative, in conscious, chronically instrumented rats. Given intravenously by 10-min infusions at doses ranging from 0.0375 to 4 micrograms/min, iloprost lowered mean arterial blood pressure in a dose-dependent and reversible fashion. The effects on blood pressure were accompanied by increases in heart rate (HR); splanchnic nerve activity (SpNA, direct recording); and mesenteric, renal, and hindlimb blood flow (Doppler probes). Doses below the depressor threshold already reduced mesenteric and hindlimb vascular resistance without affecting HR. The reduction of hindlimb resistance outlasted the iloprost infusion period. Chronic sinoaortic deafferentation (SAD) almost abolished the tachycardic reflex responses to intravenous sodium nitroprusside. The reflex increases in SpNA to intravenous iloprost were also largely prevented in SAD animals, but the tachycardic effects of iloprost persisted. In addition, neither beta 1-adrenoceptor blockade alone nor complete cardiac autonomic blockade prevented the heart rate responses to iloprost. Our results show that iloprost is a potent vasodilator that preferentially reduces hindlimb vascular resistance. Low doses of the drug increase regional blood flow without affecting blood pressure or heart rate. The tachycardic effects at higher doses cannot be explained by baroreceptor reflex (BRR) activation alone; they instead suggest a direct action on the heart. The dissociation between vasodilator and depressor effects at low doses may contribute to the therapeutic benefit of the drug in the treatment of vascular disease.

Animals↗
PubMed1988

Receptor autoradiographical evidence of a preferential reduction of binding sites for atrial natriuretic factor in renal papilla of the spontaneously hypertensive rat.

In the spontaneously hypertensive rat (SHR) as well as in the pathophysiological states with volume retention, high levels of atrial natriuretic factor (ANF) do not produce adequate diuresis and natriuresis. We have investigated the question whether the reduced effectiveness of ANF could be due to a reduction of the ANF binding. Evidence is provided by quantitative autoradiography with [125I]ANF than higher ANF plasma levels in SHRSP compared to normotensive WKY rats are associated with a reduced number of binding sites (25%) in the renal papilla as well as in the subfornical organ (69%). This could contribute to the reduced response of ANF in SHRSP.

Animals↗
PubMed1988

An approach to measuring cardiac output with Doppler flow probes in conscious rats.

The continuous measurement of cardiac output in conscious rats is difficult. Previously, Doppler flow probes have been applied to the ascending aorta by means of silicone cuffs. The placement of these cuffs can conceivably introduce errors engendered by the destruction of nerve fibers that are important in cardiac autonomic innervation. We report a novel method of Doppler flow-probe attachment directly to the ascending aorta by means of a polyacrylic cement. When we compared the response with baroreceptor activation with methoxamine and nitroprusside in conscious rats equipped either with probes attached via cuffs or directly via cement, we observed that animals equipped with cuffs failed to give the expected cardiac output and heart rate responses after nitroprusside administration. In contrast, animals that had their probes attached with cement displayed the expected responses. The data not only show that probes applied with cement give a result superior to probes attached with cuffs but also verify the suspicion that the ascending aorta is associated with nerve fibers that are important in mediating baroreceptor responses.

Animals↗
PubMed1988

Mapping of the bcl-2 oncogene on mouse chromosome 1.

Two bcl-2 alleles have been identified in inbred strains of mice by restriction fragment length polymorphism (RFLP). Analysis of a bcl-2 RFLP in a series of bilineal congenic strains (C.D2), developed as a tool for chromosomal mapping studies, revealed linkage of bcl-2 to the Idh-1/Pep-3 region of murine chromosome 1. The co-segregation of bcl-2 alleles with allelic forms of two other chromosome 1 loci, Ren-1,2 and Spna-1, in a set of back-cross progeny, positions bcl-2 7.8 cM centromeric from Ren-1,2.

Animals↗
PubMed1988

Substance P induces a cardiovascular defense reaction in the rat: pharmacological characterization.

In this study in conscious rats, we tested the hypothesis that substance P, a central pressor peptide and a potential transmitter substance of pain pathways, could be involved in the cardiovascular defense reaction that is typically associated with unpleasant sensory stimuli. The hemodynamic responses to centrally administered substance P were pharmacologically characterized. The increases in blood pressure and heart rate after intracerebroventricular injections of substance P were accompanied by mesenteric and renal vasoconstriction and hind limb vasodilation (pulsed-Doppler flow probes). The pressor and vasoconstrictor responses were attenuated by peripheral alpha 1-adrenoceptor blockade with prazosin but were not influenced by blockade of vascular vasopressin receptors with d(CH2)5Tyr(Me) arginine vasopressin (AVP). Cardiac beta 1-adrenoceptor blockade with metoprolol abolished the tachycardic and reduced the pressor responses. Substance P-induced hind limb vasodilation was not sensitive to intravenous atropine but was largely prevented by peripheral beta 2-adrenoceptor blockade with ICI 118,551. Thus, the substance P-induced pressor effects are mediated by alpha 1-adrenergic sympathetic vasoconstriction and beta 1-adrenergic cardiac stimulation, whereas the hind limb vasodilation is mainly due to beta 2-adrenergic stimulation. Substance P dose-dependently (0.01-10 micrograms i.c.v.) released oxytocin but not vasopressin or adrenocorticotropic hormone (ACTH) from the pituitary gland. High doses reduced basal ACTH levels. Together with the hemodynamic responses, a behavioral arousal reaction was observed, which included increased locomotion, grooming, scratching, and skin biting. Our results demonstrate that a neuropeptide can induce classic cardiovascular defense reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1988

Effect of high calcium diet on magnesium, catecholamines, and blood pressure of stroke-prone spontaneously hypertensive rats.

To test the effect of a high dietary calcium intake on blood pressure, we fed stroke-prone spontaneously hypertensive (SHR-SP) and Wistar-Kyoto rats (WKY) diets containing (a) 0.25% Ca/0.08% Mg, (b) 4.0% Ca/0.02% Mg, and (c) 4.0% Ca/0.08% mg, beginning at 6 weeks of age. SHR-SP and WKY rats receiving 4% Ca with the lower Mg content had lower blood pressures, hypomagnesemia, and hypomagnesuria, and grew poorly. SHR-SP receiving 4% Ca and the higher Mg diet had blood pressures no different from those of rats receiving the 0.25% Ca diet, in spite of having lower body weights. Rubidium flux studies in erythrocytes were not influenced by Ca or Mg in the diets. Plasma phosphate values were moderately reduced in rats receiving 4% Ca diets. Epinephrine and norepinephrine values were higher in SHR-SP than in WKY rats. Norepinephrine increased with stress in both strains, independent of diet. Epinephrine values were lower in SHR-SP receiving the 4% Ca diets and showed less of an increase with stress compared to SHR-SP receiving the 0.25% Ca diet. After 26 weeks of diets, SHR-SP and WKY rats were given 0.9% NaCl in their drinking water. NaCl increased blood pressure in SHR-SP irrespective of Ca content of the diet. These data suggest that a high Ca diet influences Mg homeostasis and adrenal medullary function in SHR-SP. Further, SHR-SP appear resistant to any blood pressure lowering effect of Ca irrespective of NaCl intake.

Animals↗
PubMed1988

Brain angiotensin: pathways and pharmacology.

The existence of a brain renin-angiotensin system (RAS) as one of various tissue RASs is now firmly established. Angiotensin-containing pathways within brain areas involved in central blood pressure regulation have been described. Evidence from biochemical, neurophysiologic, pharmacologic, and most recently, molecular genetic studies indicate that the brain RAS is regulated independently of the hormonal RAS and may contribute to blood pressure control and body fluid homeostasis. In addition, circulating angiotensin II can exert some of its action through stimulation of brain angiotensin receptors accessible from the blood. In experimental animal preparations of hypertension, especially in spontaneously hypertensive rats, an overactive brain RAS may be one of the factors involved in pathogenesis and maintenance of hypertension. In spontaneously hypertensive rats, inhibitors of the angiotensin II-generating converting enzyme (CE) have been shown to lower blood pressure by a central action when applied to the brain and to inhibit brain CE when applied systemically. The pathogenetic mechanisms underlying a particular cardiovascular disease and the characteristics of the CE inhibitor used (e.g., its lipid solubility governing penetration into tissue) may determine the degree to which CE inhibition within a given organ, such as the brain, contributes to the action of these drugs.

Angiotensin II↗