Search PubMed⌕ Search

Biomedical subjects

G Noll

Publications and source records attributed to G Noll.

At least 91 records · Page 5Linked to original sources
PubMed1995

Differential effects of the calcium antagonist mibefradil in epicardial and intramyocardial coronary arteries.

The efficacy of vasodilation depends on the drug and the contractile agonist involved. Furthermore, vasodilation also may be detrimental (i.e., coronary steal), possibly depending on the anatomic site and/or action of the vasodilator. We investigated the effects of Ca2+ antagonism in porcine epicardial and intramyocardial coronary arteries suspended in organ chambers filled with physiological salt solution (95% O2/5% CO2, 37 degrees C); isometric tension was measured. In epicardial vessels contracted with KCl, the thromboxane analogue U 46619, or endothelin-1 (ET-1), relaxations to the Ca2+ antagonist mibefradil were most effective after precontraction with KCl, followed by U 46619 and ET-1. In intramyocardial vessels, the contraction to KCl, U 46619, and particularly ET-1, was much more effectively inhibited by mibefradil than in epicardial arteries. In vessels preincubated with mibefradil, the drug was moderately effective in preventing the initiation of contractions. Preincubation with the inhibitor of nitric oxide production (NO), L omega-nitro arginine methyl ester (L-NAME) or endothelium removal, did not increase relaxations to mibefradil. However, epicardial but not intramyocardial vessels incubated with mibefradil exhibited enhanced relaxations to bradykinin (BK) and sodium nitroprusside (SNP) as compared with control. Thus, Ca2+ antagonism is particularly effective in intramyocardial coronary arteries. In addition to its inhibitory effects on contractility, calcium antagonism facilitates the effects of endothelium-derived NO in epicardial coronaries at the level of vascular smooth muscle (VSM).

Acetylcholine↗
PubMed1995

Effect of aging and hypertension on contractility of resistance arteries: modulation by endothelial factors.

The effects of aging and hypertension on contraction were examined in rat mesenteric resistance arteries of 12- and 74-wk-old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). The vessels were suspended in myographs (37 degrees C, 95% O2-5% CO2) filled with modified Krebs-Ringer bicarbonate solution. Isometric tension was measured. Contractions to KCl (100 mM) were similar in adult WKY and SHR; they increased in senescent WKY (P < 0.05) but decreased in senescent SHR (P < 0.05). Responses to norepinephrine (% of KCl) were comparable in all four groups. However, blockade of nitric oxide (NO) production with NG-nitro-L-arginine methyl ester (L-NAME) enhanced the sensitivity to norepinephrine in senescent animals, particularly in SHR. Inhibition of cyclooxygenase with indomethacin prevented increased sensitivity to norepinephrine after NO blockade. Responses to angiotensin (ANG) II were not affected by aging and hypertension, but the thromboxane receptor antagonist SQ-30741 reduced ANG II-induced contractions only in SHR of both ages (P < 0.05). Aging increased responses to ANG I in SHR but decreased it in WKY (P < 0.05). In quiescent rings with endothelium, acetylcholine caused contractions in the presence of L-NAME in adult and senescent SHR but not in WKY (P < 0.05). SQ-30741 prevented these contractions (P < 0.05). Contractions to the thromboxane analogue U-46619 were reduced only in senescent SHR (P < 0.05). Thus aging increases and hypertension decreases contractility of smooth muscle in rat mesenteric resistance arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Flow-diameter phase shift. A potential indicator of conduit artery function.

This study assesses (1) the relation of the very-low-frequency vasomotion (< 0.02 Hz) of the radial artery of young healthy volunteers to regional blood flow and (2) its distribution in the upper extremities. Radial artery diameters from comparable sites were measured on contralateral extremities in 18 young healthy volunteers by an echo tracking system simultaneously with blood flow velocity determined by continuous wave Doppler and blood pressure acquired by photoplethysmography in the middle finger. A synchronous global pattern of vasomotion was detected on contralateral radial arteries, suggesting the presence of either a centrally located pacemaker or a humoral system. Modulation of sympathovagal balance in 8 subjects did not significantly alter either the frequency or amplitude of the very-low-frequency vasomotor waves. Matching patterns of diameter and flow oscillations of the very-low-frequency type recorded at the same site were obtained in 10 strictly nonsmoking volunteers for given periods of time. A consistent phase lag was observed between flow and diameter signals. Flow always preceded the diameter fluctuations by a mean (+/- SEM) course of 20.8 +/- 1.56 seconds. Although the physiological basis for oscillatory behavior remains for the moment highly speculative, these results suggest that the very-low-frequency vasomotion pattern in this conduit vessel might be a flow- or shear stress-dependent phenomenon. Shear stress changes at the endothelium modulate vascular tone through the release of vasodilators. The noninvasive assessment of the diameter-flow relation may thus offer a new way of addressing vascular wall function in medium-sized and large arteries in subjects with cardiovascular risk factors.

Adult↗
PubMed1995

Nitric oxide in cardiovascular diseases.

Nitric oxide (NO), synthesized from L-arginine by a family of NO synthases (NOS), is a widespread biological mediator implicated in many physiological and pathophysiological processes, including a variety of cardiovascular diseases. Endothelium-derived NO, synthesized by a constitutive NOS, is involved in hypertension, atherosclerosis and certain heart diseases. In hypertension and atherosclerosis the role of NO is still controversial and seems to vary depending on the stage of the disease and model studied. In spontaneous hypertension, the production of NO is increased, but inefficacious, probably because of increased inactivation. In salt-induced hypertension NO production may be impaired. In atherosclerosis, an enhanced degradation of NO by superoxide radicals may explain the reduced endothelium-dependent relaxations. In pulmonary hypertension, the use of NO gas inhalation has been proposed as a future therapy for this condition. In the heart, NO regulates coronary flow and myocardial function; both functions are altered in coronary artery disease and cardiomyopathy. Nitric oxide synthesized by the inducible NOS takes part in several immunopathological diseases, such as endotoxin shock, which can particularly affect the heart. In endotoxaemia inducible NOS is overexpressed and the excess in NO production may account for the impaired cardiac performance of this condition. The overproduction of NO occurring in endotoxin shock is also responsible for the hypotension, catecholamine resistance and tissue damage characteristic of this disease. Treatment with inhibitors of NO synthesis is a promise for the future.

Arteriosclerosis↗
PubMed1995

The pathogenesis of cardiovascular disease: role of the endothelium as a target and mediator.

The cardiovascular system is regulated by the central mechanisms, hormones and local vascular mediators. Anatomically, the endothelium lies between smooth muscle cells of the blood vessel wall and the circulating platelets and monocytes. In response to mechanical and humoral signals, endothelial cells release mediators modulating contraction and proliferation of vascular smooth muscle, platelet adhesion and aggregation, coagulation and monocyte adhesion. Nitric oxide (NO), prostacyclin and a putative hyperpolarizing factor mediate relaxation. NO also inhibits smooth muscle migration and proliferation and, together with prostacyclin, platelet adhesion and aggregation. Endothelin-1, thromboxane A2 and prostaglandin H2 are endothelium-derived contracting factors. In contrast to thromboxane A2 and prostaglandin H2 which activate platelets, endothelin-1 has no direct platelet effects, but has proliferative properties in vascular smooth muscle. Under physiological conditions, the endothelium exerts vascular protective effects as it prevents adhesion of blood cells, dilates the vasculature and inhibits vascular smooth muscle proliferation. In disease states, however, endothelial dysfunction mediates vasoconstriction, adhesion of platelets and monocytes and proliferation of vascular smooth muscle cells, all events known to contribute to atherosclerotic vascular disease.

Animals↗
PubMed1994

Treatment of acute pulmonary hypertension with inhaled nitric oxide.

We examined the effectiveness of inhaled nitric oxide (NO) as a selective pulmonary vasodilator in acute pulmonary hypertension in an in vivo canine model with fixed cardiac output. In 5 dogs, total right heart bypass was instituted, and pulmonary hypertension was induced by infusion of the thromboxane analogue U-46619. During U-46619 infusion, NO was administered at 10 and 40 ppm for 5 minutes followed by breathing of the oxygen mixture without NO. Pump flow was held constant during the experiment. Infusion of the thromboxane analogue resulted in an increase in pulmonary vascular resistance and systemic vascular resistance from 147 +/- 83 to 740 +/- 126 dyne.s.cm-5 and from 1,720 +/- 113 to 2,407 +/- 232 dyne.s.cm-5, respectively. During inhalation of 10 ppm NO, pulmonary vascular resistance significantly decreased to 613 +/- 55 dyne.s.cm-5 (p < 0.05) and further decreased to 527 +/- 163 dyne.s.cm-5 with 40 ppm NO inhalation (p < 0.05). Systemic vascular resistance did not change during NO treatment (2,300 +/- 70 dyne.s.cm-5 during 40 ppm NO). There was no increase in intrapulmonary shunting or methemoglobin levels during NO inhalation. In this setting, with a constant cardiac output throughout the experiment, NO acted as a selective pulmonary vasodilator without altering systemic vascular resistance. However, induced pulmonary vasoconstriction was only partially reversed by NO inhalation.

Acute Disease↗
PubMed1994

Influence of lipoproteins on endothelial function.

The endothelium is a physical barrier between the blood and vascular smooth muscle, a source of enzymes activating and deactivating cardiovascular hormones and a site of production of relaxing and contracting factors. Nitric oxide is a potent vasodilator and inhibitor of platelet function which under most circumstances is released together with prostacyclin which exerts similar effects. Both substances play an important protective role in the coronary circulation in that they cause continuous vasodilation and inhibition of platelet function. In addition, the endothelium is a source of contracting factors such as endothelin-1, thromboxane A2 and endoperoxides. Due to its strategic anatomic position, the endothelium is a primary target of injuries and cardiovascular risk factors. Besides other risk factors such as hypertension and diabetes, low density lipoproteins alter endothelial function. A reduced release of endothelium-derived relaxing factors and an enhanced liberation of endothelium-derived contracting factors are common in the presence of lipoproteins. These alterations in endothelial function are likely to contribute to the pathogenesis as well as progression and complications of coronary artery disease such as vasospasm and thrombus formation. This review will focus on the influence of lipoproteins on endothelial function.

Animals↗
PubMed1994

Endothelial dysfunction in aorta of the spontaneously hypertensive, stroke-prone rat: effects of therapy with verapamil and trandolapril alone and in combination.

The effects of chronic therapy with the angiotensin-converting enzyme (ACE) inhibitor trandolapril and/or Ca2+ antagonist verapamil on endothelial and vascular smooth muscle (VSM) function were studied in spontaneously hypertensive, stroke-prone rats (SHRSP). Dosages decreasing systolic blood pressure (SBP) by 20% were administered orally (p.o.) by gavage as monotherapy or combination therapy for 8 weeks, beginning at age 6 weeks. Combination therapy dosages were the same as those used in monotherapy (trandolapril 0.7 mg/kg/day verapamil 20 mg/kg/day) in one group; the second group received only half the monotherapy dosage. The study was placebo-controlled and performed in parallel groups. Isometric tension was measured in aortic rings suspended in organ chambers (95% C2/5% CO2; 37 degrees C). SBP decreased in all groups, as compared with placebo [30-47 mm Hg, analysis of variance (ANOVA), p < 0.05], but decrease was more pronounced in rats receiving high-dose combination (76 mm Hg, ANOVA, p < 0.05). In norepinephrine (NE)-contracted rings, endothelium-dependent relaxation to acetylcholine (ACh) was augmented similarly with all forms of therapy (maximal relaxations 89-94%) as compared with placebo (64 +/- 6%, p < 0.05). In contrast, the response to sodium nitroprusside (SNP) was similar in all groups (NS). In quiescent rings, ACh elicited endothelium-dependent contractions (in the presence of N omega-monomethyl-L-arginine, L-NAME) that were not affected by therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Skin sympathetic nerve activity and effector function during sleep in humans.

Multi-unit sympathetic skin nerve activity (SSA) in the peroneal nerve was recorded together with electrical skin resistance, skin blood flow and (in some subjects) finger blood pressure during sleep in 22 sleep-deprived healthy subjects. The average strength of sympathetic activity in different sleep stages was measured during 5-min periods as the area-under-curve of the integrated neurogram. Stage 2 sleep was reached by 15 subjects, stages 3-4 by nine and rapid eye movement (REM) sleep by six subjects. Non-REM sleep was always associated with an increased skin resistance, which was larger in glabrous than in hairy skin (293 +/- 48 vs. 175 +/- 4% of awake control level, n = 10, P < 0.05). Skin blood flow also increased during sleep, with a mean maximal increase of 397 +/- 79% of the awake control level (n = 11, P < 0.05). In spite of these changes of effector function no significant difference in mean SSA was found between the awake control period and periods of non-REM sleep, but during REM sleep SSA increased with 34% (P < 0.05) compared with the immediately preceding stage 2 period. In stage 2 sleep, K-complexes were associated with bursts of SSA followed by transient changes of skin resistance, blood flow and arterial blood pressure. When both skin resistance and blood flow were recorded within the innervation area of the impaled fascicle, single bursts or short periods of increased SSA could be succeeded by increased skin blood flow without concomitant skin resistance change. This indicates the existence of specific sympathetic vasodilator fibres in the skin. Therefore the unchanged strength of multiunit SSA during non-REM sleep in the face of increases of skin resistance and blood flow may be a consequence of an increased sympathetic vasodilator nerve activity combined with decreases of vasoconstrictor and sudomotor traffic.

Adult↗
PubMed1994

Alterations in coronary artery vascular reactivity of hypertensive Ren-2 transgenic rats.

BACKGROUND: The renin-angiotensin system and endothelium-derived nitric oxide (EDNO) are important regulators of vascular tone. This study was designed to investigate endothelial and vascular smooth muscle function in coronary arteries of Ren-2 transgenic rats. METHODS AND RESULTS: Left anterior descending coronary arteries and aortas were isolated from transgenic rats and Sprague-Dawley control rats at 6 (young) and 12 (adult) weeks of age and examined in myographs or organ chambers for isometric tension recording. Systolic blood pressure was significantly higher in transgenic rats (young, 229 +/- 6 mm Hg; adult, 239 +/- 8 mm Hg) than in control rats (young, 126 +/- 2 mm Hg; adult, 118 +/- 3 mm Hg; P < .005). N omega-Nitro-L-arginine methyl ester (L-NAME, 10(-7) to 10(-4) mol/L) evoked marked endothelium-dependent contractions in coronary arteries (young, 52 +/- 8% of the contraction to 100 mmol/L KCl; adult, 40 +/- 8%) but not aortas (young, 3 +/- 1%; adult, 2 +/- 1%). In coronary arteries, this response was significantly smaller in adult (n = 9) than in young (n = 8, P < .05) control rats. Young transgenic rats (56 +/- 9%, n = 8) showed slightly stronger contractions in response to L-NAME than young control rats (NS), which almost totally disappeared in adult transgenic rats (6 +/- 3%, n = 7; P < .05 versus adult control rats; P < .01 versus young transgenic rats). Endothelium-dependent relaxations in response to acetylcholine (10(-9) to 10(-4) mol/L) were totally blocked by L-NAME (10(-4) mol/L) but were unaffected by the thromboxane receptor antagonist SQ30741 (10(-7) mol/L). This stimulated release of EDNO, endothelium-independent relaxations in response to the nitrovasodilator linsidomine (10(-9) to 10(-5) mol/L), and contractions in response to KCl (100 mmol/L) were comparable in all groups of rats. CONCLUSIONS: Ren-2 transgenic rats develop fulminant hypertension that is associated with a selective decrease in endothelium-dependent contractions in response to L-NAME, whereas endothelium-dependent relaxations in response to acetylcholine as well as smooth muscle function remain unaffected.

Acetylcholine↗
PubMed1994

Endothelin receptor antagonists inhibit endothelin in human skin microcirculation.

Endothelin is a potent vasoconstrictor peptide produced by endothelial cells, but its role in physiology and disease is uncertain. We investigated the influence of the endothelin-A-selective receptor antagonist PD 147953 and the nonselective endothelin receptor antagonist PD 145065 on the effects of endothelin-1 and endothelin-3 in the skin microcirculation of healthy volunteers, using laser Doppler flowmetry. A double injection model was developed, allowing simultaneous injection of two substances, ie, agonist and antagonist or saline. The injection of saline led to a well-defined vasodilation at the injection site (maximum increase, from 19 +/- 2 to 97 +/- 15 perfusion units at 6 minutes; P < .001; n = 10). Endothelin-1 (10(-12) mol) decreased blood flow (difference from saline control, -79 +/- 14 perfusion units; P < .001; n = 11) within the injection wheal (diameter, 4 to 5 mm), while endothelin-3 had no effect. In the surrounding area (at 8 mm from the injection site), both endothelin-1 (+116 +/- 32 perfusion units; P < .001; n = 11) and endothelin-3 (+59 +/- 16 perfusion units; P < .001; n = 11) markedly increased blood flow. Both endothelin receptor antagonists slightly increased blood flow (maximum difference from control, +56 +/- 18 [PD 147953] and +31 +/- 10 [PD 145065] perfusion units; P < .05; n = 8) and inhibited endothelin-1-induced (P < .01) vasoconstriction. The vasoconstriction to norepinephrine was not affected by the endothelin antagonist PD 147953. Endothelin-1- and endothelin-3-induced vasodilation in the surrounding area were also inhibited by both endothelin antagonists or by lidocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Activity of the L-arginine/nitric oxide pathway and endothelin-1 in experimental heart failure.

Neurohumoral changes influencing peripheral vascular resistance play a major role in congestive heart failure (CHF). We studied vascular function in 1-year-old cardiomyopathic syrian hamsters with pulmonary congestion and age-matched control hamsters. Aorta and mesenteric resistance arteries were suspended in organ chambers and myographs, respectively, for isometric tension recording. In aorta and mesenteric resistance arteries, contractile responses to norepinephrine (NE) were comparable in cardiomyopathic hamsters and controls. After inhibition of nitric oxide (NO) formation with nitro-L-arginine methylester (L-NAME), contractions to NE were enhanced in aorta of cardiomyopathic hamsters (p < 0.05); no effect was noted in controls or mesenteric resistance arteries. Low doses of endothelin-1 (ET-1 10(-10)-10(-9) M) caused stronger contractions in aorta of cardiomyopathic hamsters as compared with controls (p < 0.05). The sensitivity and maximal contraction to ET were more pronounced in mesenteric resistance arteries as compared with aorta in both cardiomyopathic and control hamsters (p < 0.05-0.001). In both aorta and mesenteric resistance arteries, acetylcholine (ACh 10(-9)-10(-5) M) induced concentration-dependent relaxation, which was prevented by L-NAME (p < 0.001). Maximal endothelium-dependent relaxation was more pronounced in aorta of cardiomyopathic hamsters (p < 0.05), but not different in mesenteric resistance arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Endothelium dysfunction in the coronary circulation.

Coronary artery disease is the most important cause of morbidity and mortality in Western countries. Its pathogenesis is unknown but involves an enhanced vasoconstriction and increased interaction of platelets and monocytes with the vessel wall, as well as proliferation, migration, and extracellular matrix formation of vascular smooth-muscle cells. The endothelium lies in a strategic anatomical position between the circulating blood and vascular smooth-muscle cells. This supports the concept that dysfunction of these cells plays a crucial role in the pathogenesis of coronary artery disease. Endothelial cells are a source of vasodilators such as nitric oxide, prostacyclin, and hyperpolarizing factor. In addition, the cells produce heparin-like substances as well as other molecules with antiproliferative properties. These effects of endothelial cells may explain why platelets and monocytes usually do not adhere at the blood vessel wall and why vascular smooth-muscle cells remain in a vasodilated state and neither migrate nor proliferate. However, under pathological conditions, in particular in the presence of cardiovascular risk factors, endothelial dysfunction occurs and significantly contributes to the increase of platelet-vessel wall interaction, vasoconstriction, and proliferation in the coronary system. Under these conditions, endothelium-dependent vasodilation is reduced and endothelium-dependent constrictor responses are augmented. Furthermore, endothelial cells are also able to produce growth promoters. Hence, endothelial cells are important targets and mediators of coronary artery disease. Therapeutic strategies aimed at improving or preserving endothelial function therefore may be promising in the prevention and treatment of coronary artery disease.

Animals↗
PubMed1993

Endothelial dysfunction in coronary artery disease.

The endothelium is a physical barrier between the blood and vascular smooth muscle, a source of enzymes activating and deactivating cardiovascular hormones and a site of production of relaxing and contracting factors. In addition, the endothelium is a source of growth inhibitors and promoters of vascular smooth muscle cells. Monoaminooxidase deactivates catecholamines and serotonin. Angiotensin converting enzyme transforms angiotensin I into angiotensin II and breaks down bradykinin into inactive products. Nitric oxide is a potent vasodilator and inhibitor of platelet function that under most circumstances is released together with prostacyclin, which exerts similar effects. Both substances play an important protective role in the coronary circulation in that they cause continuous vasodilation and inhibition of platelet function. In addition, the endothelium is a source of contracting factors such as endothelin-1, thromboxane A2, and endoperoxides. Endothelium-derived growth inhibitors include heparin (sulfates) and transforming growth factor beta 1, while basic fibroblast growth factors and platelet-derived growth factor and possibly endothelin promote proliferation. Because of its strategic anatomic position, the endothelium is a primary target for injuries and cardiovascular risk factors. In particular, aging, low density lipoproteins, hypertension, diabetes, and ischemia alter endothelium function. In arterial coronary bypass grafts, the release of nitric oxide is more pronounced than in vein grafts. Alterations of endothelial function may contribute to vasospasm, thrombus formation, and vascular proliferation and in turn myocardial ischemia, all common events in patients with coronary artery disease.

Coronary Circulation↗
PubMed1993

Calcium antagonists differently inhibit proliferation of human coronary smooth muscle cells in response to pulsatile stretch and platelet-derived growth factor.

BACKGROUND: Vascular smooth muscle cell proliferation is the key event of coronary artery disease. Mechanical forces, in particular, pulsatile stretch and platelet-derived growth factor, may play an important role. METHODS AND RESULTS: Vascular smooth muscle cells were cultured from the media of human left descending coronary arteries obtained from organ donors using the explant method. To study effects of pulsatile stretch on vascular smooth muscle cell proliferation, a computer-controlled in vitro pulsatile stretch device was used. Cells were seeded onto Flex I culture plates with deformable membranes and exposed to pulsatile stretch (60 cycles per minute) and/or growth factors. Proliferation of smooth muscle cells was determined by 3H-thymidine incorporation. Pulsatile stretch markedly stimulated 3H-thymidine incorporation of coronary smooth muscle cells (180 +/- 15 to 432 +/- 27 cpm/10(5) cells; P < .05) after 24 hours and increased cell number after 6 days (10.3 +/- 0.7 x 10(4)/mL; P < .05). Platelet-derived growth factor-AB (0.01 to 10 ng/mL) concentration-dependently stimulated 3H-thymidine incorporation in coronary smooth muscle cells (EC50, 0.1 ng/mL) and had additive effects with pulsatile stretch. The Ca2+ antagonist verapamil (10(-7) to 10(-5) M) concentration-dependently inhibited proliferation stimulated by platelet-derived growth factor back to control levels (P < .05 to .01) but not that induced by pulsatile stretch. CONCLUSIONS: Pulsatile stretch and platelet-derived growth factor are potent stimuli for proliferation of coronary smooth muscle cells. The selective inhibitory effect of a Ca2+ antagonist on smooth muscle cell proliferation stimulated by platelet-derived growth factor but not by pulsatile stretch may explain why the drugs have only modest antiatherogenic effects in patients with coronary artery disease.

Cell Division↗
PubMed1992

[Drug-induced hyperprolactinemia and galactorrhea].

A 21 year old female treated for recurring gastric troubles with dopamine-antagonists (domperidone, metoclopramide) developed a clinically manifest hyperprolactinemia (3055 microU/l; normal value < 650 microU/l) with galactorrhea only two days after a new two day course of metoclopramide. The drug was withdrawn and within days mastodynia and galactorrhea subsided. A control of plasmatic prolactin two weeks later yielded a normal value (358 microU/l). After administration of metoclopramide or domperidone hyperprolactinemia is regularly observed and galactorrhea has been described earlier. It is unclear why this patient inspite of repeated administration of one dopamine antagonist remained asymptomatic whereas the other after a short time and only a few doses led to galactorrhea. It is conceivable that differences in passage into the cerebrospinal fluid or the better penetration of the blood-brain barrier favored the development of galactorrhea under metoclopramide. This case served to discuss the pathophysiologic background of drug-induced hyperprolactinemia.

Adult↗
PubMed1992

[Clinical-pharmacological case report: drug-induced inappropriate ADH secretion].

The syndrome of inadequate secretion of antidiuretic hormone (SIADH) following treatment with a tricyclic antidepressant is demonstrated using the example of a 70 year-old man admitted for weakness and cognitive disturbances. Because of incontinence he had been periodically treated since 1989 with imipramine (Tofranil) by his family doctor. On admission he was seriously hyponatriemic and had low plasmatic osmolality, significantly lower than urinary osmolality. Creatinine, urea and uric acid in serum were also below normal values. Like other drugs tricyclic antidepressants can rarely induce an increased release of ADH by direct hypothalamic stimuli. In this patient imipramine was terminated and within a few days of reduced fluid intake and substitution of sodium a sustained clinical improvement and normalisation of laboratory parameters was noted. The patient was discharged to his home after three weeks.

Aged↗