Biomedical subjects

C Sernia

Publications and source records attributed to C Sernia.

At least 55 records · Page 3Linked to original sources

PubMed1994

A novel inhibitory role for glucocorticoids in the secretion of angiotensinogen by C6 glioma cells.

Astrocytes have been identified as the primary source of brain angiotensinogen (Ao), but the regulation of the secretion of this protein from astrocytes is poorly defined. In this study, the rat C6 glioma cell line was used as an astrocyte model to investigate the regulation of Ao secretion. C6 cultures secreted Ao at a rate of 4.05 +/- 1.52 (mean +/- SD) ng of Ao/10(6) cells/24 h as determined by a direct radioimmunoassay. This rate was not significantly altered by the hormones thyroxine, estradiol, angiotensin II, growth hormone, and prostaglandins or by increased levels of intracellular cyclic AMP. Treatment with the synthetic glucocorticoid dexamethasone (DEX; 10(-6) M) reduced the rate of Ao secretion to 1.82 +/- 0.28 ng of Ao/10(6) cells/24 h. By comparison, the basal secretion rate for rat H4 hepatoma cells was 142.4 +/- 10.0 ng of Ao/10(6) cells/24 h, and this increased fourfold (572.4 +/- 173.1 ng/10(6) cells/24 h) in the presence of 10(-6) M DEX. Both these inhibitory (C6) and stimulatory (H4) actions of DEX were dose related. The inhibition observed in C6 cells was mimicked by RU28362, a pure glucocorticoid agonist, and reversed by the antagonist RU486, demonstrating that DEX was functioning as a true glucocorticoid. The action of DEX was also antagonized by the cyclic AMP analogue N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (dBcAMP) (control, DEX, and DEX + dBcAMP, 3.58 +/- 0.73, 1.69 +/- 0.82, and 4.93 +/- 1.88 ng of Ao/10(6) cells/24 h, respectively, and by the beta-adrenergic agonist isoprenaline, which stimulates cyclic AMP production.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

PubMed1994

Angiotensin receptors in cardiovascular diseases.

1. Angiotensin II (AII) plays a major role in cardiovascular function via direct actions on the vasculature, kidney, adrenal, heart, brain and sympathetic nerves. The cellular effects of AII are extensive and encompass hypertrophy, hyperplasia and the deposition of extracellular matrix. 2. The actions of AII are mediated by the AT1 and AT2 membrane receptor subtypes, and additional forms of each subtype. Evidence is emerging that selective changes in AII receptor subtypes occur in cardiovascular diseases. 3. Thyroid dysfunction increased cardiac, liver and kidney AII receptor density but decreased adrenal gland receptor density. In the heart, there was a selective increase in AT2 receptor density. 4. Diabetes increased cardiac, liver and adrenal gland AII receptor densities but decreased kidney receptor density. 5. Hypertension increased AII receptor density in the heart and kidney. A corresponding increase in receptor mRNA was prevented by selective AT1 receptor antagonists. 6. The human heart contained AII receptors in all chambers; right atrial receptor density was increased in coronary artery bypass graft patients. 7. The presence of AII receptor changes in these models of cardiac hypertrophy and hypertension raises the possibility of using orally active, subtype-selective agonists and antagonists to treat particular forms of cardiovascular diseases.

Acromegaly↗

PubMed1994

Characterization and localization of oxytocin receptors in the rat testis.

In this study oxytocin (OT) receptors have been characterized and localized in the testis of the rat using the radioiodinated OT receptor antagonist 125I-labelled d(CH2)5 [Tyr(Me)2,Thr4,Tyr9-NH2]-vasotocin (OTA). Receptor density and localization have been compared with the rat testis arginine vasopressin (AVP) receptor using the radioiodinated AVP V1a receptor antagonist 125I-labelled d(CH2)5Sar7-AVP and the radioiodinated linear AVP V1a antagonist 125I-labelled [(C6H5-CH2CO)-O-methyl-D-Tyr-Phe-Gln-Asn-Arg-Pro- Arg-Pro-Arg-Tyr-NH2]. 125I-labelled OTA bound with high affinity to membrane fractions of the rat testis (Ka = 13.8 +/- 1.25 litres/nmol), mammary tissue (Ka = 20.3 +/- 4.36 litres/nmol) and uterus (Ka = 27.8 +/- 0.74 litres/nmol). Competition studies with various OT and AVP receptor agonists and antagonists confirmed that the binding was to OT receptors. AVP receptors in the testis were found to be identical to AVP V1a receptors in the liver. The AVP receptor density in the testis was much higher than the OT receptor density (109 +/- 12.3 vs 5.2 +/- 0.79 (mean +/- S.E.M.) fmol/mg protein). Autoradiographical localization showed that both OT and AVP receptors were present in the interstitial spaces in the testis consistent with binding to Leydig cells. AVP receptors were also localized on the epithelial surfaces of the seminiferous tubules and on testicular blood vessels. This study has, for the first time, found OT receptors in the testis of the rat which have similar ligand-binding characteristics to mammary and uterine OT receptors. The receptor localizations are consistent with binding to Leydig cells.

Animals↗

PubMed1994

Beta-adrenoceptor antagonism and the hyperthyroid rat heart.

beta-Adrenoceptor antagonists such as propranolol and atenolol ameliorate the symptoms of human hyperthyroidism. We wished to define whether the cardiac changes of hyperthyroidism are attenuated by treatment with the beta-adrenoceptor antagonist atenolol. Rats were treated with triiodothyronine (T3) [1 mg/kg/day subcutaneously (s.c.) for 14 days] together with oral atenolol (100 mg/day on days 8-14); physiological parameters, inotropic and chronotropic responses in isolated cardiac tissues to compounds that increase intracellular cyclic AMP, and ventricular beta 1- and beta 2-adrenoceptors were measured. Administration of T3 produced marked hyperthyroidism, leading to increased metabolism, cardiac hypertrophy, tachycardia, hypertension, marked decrease in or loss of positive inotropic responses to calcium chloride, norepinephrine (NE), forskolin, and theophylline and increased ventricular beta 1- and beta 2-adrenoceptor density. Atenolol treatment of hyperthyroid rats attenuated the increases in heart rate (HR), rectal temperature, and O2 consumption but did not alter cardiac hypertrophy, hypertension, decreased positive inotropic responses or increased beta-adrenoceptor density. We conclude that beta-adrenoceptor antagonists produce only limited changes in hyperthyroidism-induced cardiovascular responses; furthermore, beta-adrenoceptor antagonists are unlikely to attenuate the cardiovascular risk factors of hyperthyroidism.

Adrenergic beta-Antagonists↗

PubMed1993

Adrenoceptor-mediated cardiac and vascular responses in genetically growth hormone-deficient rats.

This study has measured cardiovascular parameters, pharmacological responses to alpha- and beta-adrenoceptor agonists, and cardiac beta-adrenoceptor characteristics in growth hormone (GH)-deficient (dwarf) Lewis rats, normal Lewis rats and dwarf rats treated with GH (2 mg/kg/day for 28 days). Dwarf rats showed a decrease mean blood pressure and heart rate but an increased ventricular weight relative to body weight when compared with age-matched normal Lewis rats. Positive chronotropic responses in vivo to the non-selective beta-adrenoceptor agonist, isoprenaline, were unchanged in dwarf rats. The selective beta 1-adrenoceptor agonist, noradrenaline, was less potent in isolated right atria from dwarf rats although maximal responses were unchanged. Basal force of contraction was greater in isolated cardiac muscles from dwarf rats than from normal rats. Maximal positive inotropic responses to both calcium chloride and noradrenaline were reduced in left atria but increased in left ventricular papillary muscles from dwarf rats. Responses to the alpha 1-adrenoceptor agonist, phenylephrine, were markedly increased in isolated cardiac tissues from dwarf rats. Maximal contractile responses of isolated thoracic aortic rings from dwarf rats to KCl (100 mM) and the alpha-adrenoceptor agonist, noradrenaline, were markedly reduced compared to responses in normal rats. Left ventricular beta-adrenoceptor density measured by 125I-cyanopindolol binding was significantly increased in dwarf rats. Administration of GH (2 mg/kg/day for 28 days) reversed the altered responses in dwarf rats. We conclude that GH: (a) is required for the development of normal contractile capability of cardiac and vascular tissues; (b) regulates both beta-adrenoceptors and alpha- and beta-adrenoceptor-mediated responses; (c) differentially regulates atrial and ventricular responsiveness.

Animals↗

PubMed1993

Posterior pituitary of the newborn marsupial possum, Trichosurus vulpecula.

The fetal anterior pituitary-adrenal axis is thought to be involved in the initiation of birth in both eutherian and marsupial mammals. Little is known about the structure and function of the posterior pituitary at birth in the marsupial. Immunocytochemistry, high pressure liquid chromatography, and radioimmunoassay were used to identify vasopressin and mesotocin in the posterior pituitary of a newborn marsupial, the brushtail possum, Trichosurus vulpecula. The concentrations of vasopressin and mesotocin in the head of the newborn possum were 0.34 and 0.28 ng, respectively. The concentration of vasopressin was always greater than that of mesotocin, and the amounts of neuropeptides present in the head increased as the possum developed.

Aging↗

PubMed1993

The ultrastructure of the prothoracic gland/corpus allatum/corpus cardiacum ring complex of the Australian sheep blowfly larva Lucilia cuprina (Wied.) (Insecta: Diptera).

The ultrastructure of the constituent endocrine glands within the ring complex of Lucilia cuprina larvae has not been previously described. This study investigated the ring complex of mid-third instar larvae. Three distinct endocrine cell types were identified: (1) prothoracic gland (PTG) cells which constituted the major cell type; (2) corpus allatum (CA) cells, localized in the anterior central region, and (3) corpus cardiacum (CC) cells, located posteriorly, ventral to the aorta. PTG cells were identifiable by their large ovoid nuclei (9-14 microns dia, length 12-18 microns) and numerous cytoplasmic lipid vacuoles. The plasma membrane of peripheral PTG cells were invaginated to form intercellular channels. The CA cells are characterized by ovoid nuclei (6-7.5 microns dia, 6.5-9 microns length) and electron dense staining cytoplasm. Compared to PTG cells the CA cells had smaller nuclei and lower nucleus:cytoplasm cell ratio. Extensive networks of highly irregular, electron-lucent intracellular spaces, dispersed throughout the cytoplasm were also characteristic of CA cells at this developmental stage. These spaces often contained membrane bound lipid vacuoles occurring singly or as aggregates. The CC contained both intrinsic and extrinsic neural components. The intrinsic cells were characterized by circular nuclei (6.5-8.5 microns dia), prominent nucleolus and numerous cytoplasmic electron-dense neurosecretory granules (100-240 nm dia). The extrinsic axons and terminals within the CC contained electron-dense neurosecretory granules (80-150 nm), neurotubules and mitochondria.

Animals↗

PubMed1993

Cardiac angiotensin receptors in experimental hyperthyroidism in dogs.

OBJECTIVE: The aim was to define the changes in angiotensin II receptors and the plasma renin-angiotensin system in experimental hyperthyroidism in dogs. METHODS: Hyperthyroidism was induced in dogs by subcutaneous injection of triiodothyronine (T3; 1 mg.kg-1 x d-1 for 14 d; group T); control dogs received saline (group C). Plasma angiotensin II (AII), angiotensinogen, renin activity and concentration, and angiotensin II receptors in left ventricle, right atrium, thoracic aorta, adrenal gland, and liver were measured. RESULTS: T3 treatment caused tachycardia, increased heart weight, hypertrophy of the circumflex and septal coronary arteries, increased plasma renin activity [C = 1.6(SEM 0.2), T = 9.8(2.8) ng angiotensin I.ml-1 x h-1], plasma renin concentration [C = 13.0(3.7), T = 34.5(5.6) ng angiotensin I.ml-1 x h-1], and plasma AII [C = 23(3), T = 104(5) pg.ml-1], while plasma angiotensinogen did not change. There were no significant changes in adrenal gland and right atrial angiotensin II receptor densities; increases were measured in the left ventricle [C = 0.33(0.06), T = 0.75(0.12) pmol.g-1 tissue], thoracic aorta [C = 0.19(0.02), T = 0.28(0.03) pmol.g-1 tissue], and liver [C = 8.4(1.2), T = 12.9(1.7) pmol.g-1 tissue]. The relative affinities of the left ventricular angiotensin II receptor for angiotensin peptides (obtained from displacement assays) were: Sar1, Ile8-AII > AII > angiotensin III > angiotensin I > hexapeptide > pentapeptide. CONCLUSIONS: Experimental hyperthyroidism in dogs results in activation of the plasma renin-angiotensin system and up regulation of left ventricular, aortic, and liver angiotensin II receptors.

Animals↗

PubMed1993

Renin-angiotensin system in thyroid dysfunction in rats.

Thyroid dysfunction produces marked cardiovascular responses; the renin-angiotensin system (RAS) is important in control of the cardiovascular system. We have measured changes in the plasma RAS and in angiotensin II (AT) receptors in experimentally hyperthyroid, euthyroid, or hypothyroid rats. Hyperthyroidism activated the plasma RAS, increasing plasma angiotensinogen by 85% after 7-day triiodothyronine (T3) treatment, plasma renin activity (PRA) by 47% and concentration by 52%, and plasma AT by 1.250%. Hypothyroidism reduced plasma angiotensinogen by 71%, PRA by 73%, and plasma AT by 81% without altering plasma renin concentration (PRC). Plasma aldosterone was reduced by 39% in hyperthyroid rats and by 95% in hypothyroid rats. AT receptors were characterized in heart, liver, adrenal gland, and kidney. Cardiac, liver, and kidney AT receptor densities increased in hyperthyroidism by 73, 113, and 75%, respectively; adrenal gland receptor density decreased by 39%. Similar results were observed in hypothyroidism except that adrenal gland receptor density was markedly increased by 205%. AT receptor subtypes were characterized in ventricular homogenates by the selective antagonist losartan. Hyperthyroidism markedly increased AT2-subtype density by 204% in left ventricle, and by 304% in right ventricle and decreased AT1-subtype density by 38% and 31% in left and right ventricles, respectively. AT2-subtype density increased by 168% in hypothyroid rats; AT1-subtype density was unchanged. Thyroid dysfunction causes significant changes in the RAS and in AT receptor density, especially of the AT2 subtype. Although a physiological function has not yet been reported for AT2 receptors, our results suggest that selective AT2-receptor antagonists may prove therapeutically useful in treatment of cardiovascular disease in thyroid dysfunction.

Adrenal Glands↗

PubMed1993

Effects of different oral oestrogen formulations on insulin-like growth factor-I, growth hormone and growth hormone binding protein in post-menopausal women.

OBJECTIVE: Insulin like growth factor-I (IGF-I) levels in post-menopausal women are reduced by oral administration of the synthetic oestrogen ethinyl oestradiol but increased by transdermal delivery of 17 beta-oestradiol. Since these oestrogen types are different, the aim of this study was to clarify whether reduction in IGF-I is a specific effect of ethinyl oestradiol or common to other oral oestrogen formulations. DESIGN: Randomized cross-over study comparing one month of treatment with ethinyl oestradiol (20 micrograms), conjugated equine oestrogen (1.25 mg Premarin) and oestradiol valerate (2 mg). SUBJECTS: Six healthy post-menopausal women, age 60.3 +/- 5.6 years. MEASUREMENTS: Mean 24 hour GH (from hourly sampling), IGF-I, GH binding protein (GHBP), pituitary (LH, FSH) and hepatic function (SHBG and angiotensinogen) were measured. RESULTS: All three oestrogen formulations resulted in a significant reduction in IGF-I levels compared to baseline and significant elevations of GH and GHBP (P < 0.05). The percentage increase in GH during oestrogen treatment was significantly related to the percentage decrease in IGF-I levels (P = 0.04). All three oestrogen formulations resulted in significant suppression of LH and FSH and induction of the hepatic proteins, SHBG and angiotensinogen (P < 0.05). GHBP increased in parallel with other hepatic proteins. CONCLUSIONS: Reduction in IGF-I levels is an intrinsic effect of oral oestrogen therapy and increased GH levels may occur as a result of reduced feedback inhibition by IGF-I. Since GHBP activity is not changed by transdermal oestrogen, we conclude that the liver is a major source of circulating GHBP and that GHBP is an oestrogen sensitive protein.

Aged↗

PubMed1993

Stimulation of the renin-angiotensin system by growth hormone in Lewis dwarf rats.

A genetically growth hormone (GH)-deficient strain of Lewis rats was used to test the hypothesis that the actions of GH on electrolyte and fluid homeostasis are mediated by the renin-angiotensin-aldosterone system (RAAS). Dwarf rats injected with recombinant bGH (2 mg.kg-1 x day-1) for 7 days (group GH1+) and 28 days (group GH4+), respectively, were compared with saline-injected dwarf (group GH-) and normal (group N) Lewis rats. GH decreased Na+ excretion and increased renal glomerular filtration rate in dwarf rats. The dietary intake and plasma concentrations of Na+ and K+ remained unchanged. GH increased plasma insulin-like growth factor I (IGF-I) concentrations in dwarf rats (GH - = 109 +/- 9, GH1+ = 184 +/- 5, GH4+ = 189 +/- 28, N = 477 +/- 29 ng/ml plasma). Plasma angiotensinogen increased towards the levels found in normal Lewis rats (GH- = 859 +/- 38, GH1+ = 906 +/- 18, GH4+ = 1,027 +/- 19, N = 1497 +/- 80 ng angiotensin I/ml plasma); plasma renin activity increased above that of the normal Lewis (GH- = 10.2 +/- 0.6, GH1+ = 11.7 +/- 0.7, GH4+ = 16.7 +/- 2.4, N = 10.6 +/- 0.8 ng angiotensin I.ml plasma-1 x h-1). Plasma aldosterone, corticosterone, and triodothyronine concentrations were unchanged by GH treatment. Angiotensin II receptor densities in GH- rats (liver = 356 +/- 23, kidney = 228 +/- 28, adrenal = 478 +/- 58 fmol/mg protein) were upregulated by GH (GH4+ rats; liver = 573 +/- 27, kidney = 360 +/- 86, adrenal = 721 +/- 78 fmol/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effect of photoperiod on the breeding season of the marsupial possum Trichosurus vulpecula.

The production of young by three groups of eight possums, housed in a natural, a short-day (10 h light:14 h dark) and a long-day (14 h light:10 h dark) photoperiod was monitored for 24 months to determine the role of photoperiod on the occurrence and duration of the breeding season. Possums were housed in each of the three light regimens on 22 November. The possum has a gestation duration of 17.5 days. Removal of the newborn young leads to ovulation approximately 9 days later and birth 26 days later. Repeated removal of pouch young was used to determine the duration of the breeding season. Possums in a natural photoperiod showed two breeding seasons for the 2 year observation, from March to October of each year. Over the same 2 year period, there were three breeding periods in possums in short-day and long-day photoperiod. A comparison of the timing of the first breeding season showed that short-day photoperiod brought the breeding season forward by 2 months and long-day photoperiod delayed it by 2.5 months. The total number of months in which births occurred was the same for natural and short-day photoperiod (16 out of 24 months) and less for long-day photoperiod (11 months). Fertility in the three groups was also examined. Within each group, there was no change in fertility with consecutive seasons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Angiotensinogen is secreted by pure rat neuronal cell cultures.

Previous studies are divided between those which support a neuroglial (astrocyte) source for brain angiotensinogen and those which indicate that both astrocytes and neurones synthesize the precursor of angiotensin II. In this study, separate cultures of astrocytes and neuronal cells were prepared and established as being essentially pure by appropriate immunocytochemical cell markers. Angiotensinogen production by these cultures, as measured by a direct radioimmunoassay, was 20.74 +/- 3.62 ng angiotensinogen/10(6) cells/24 h (mean +/- S.D., n = 8) for astrocytes and 4.39 +/- 0.94 ng/10(6) cells/24 h (mean +/- S.D., n = 29) for neurones. Angiotensinogen secretion from both cell types was unaffected by treatments which stimulate the regulatory secretory pathway by modulating intracellular cAMP levels. In contrast, it was reduced from 23.20 +/- 2.14 to 8.14 +/- 1.31 ng/10(6) cells/24 h (S.E.M., n = 7) in astrocyte cultures by the constitutive pathway inhibitor, monensin. Angiotensinogen secreted by astrocytes and neurones was compared to pure angiotensinogen and that in plasma and cerebrospinal fluid (CSF) by cation-exchange mono S column chromatography. Pure angiotensinogen eluted as two separate peaks corresponding to the major forms of plasma angiotensinogen, whereas angiotensinogen in CSF and culture media coeluted with a third minor form of plasma angiotensinogen. It was concluded that neuronal cells as well as astrocytes secrete angiotensinogen which is distinctly different from plasma angiotensinogen.

Angiotensinogen↗

PubMed1992

Brain content and plasma concentrations of arginine vasopressin in an Australian marsupial, the brushtail possum Trichosurus vulpecula.

Arginine vasopressin (AVP) has been identified and quantified in the brain and plasma of the possum using a highly specific radioimmunoassay and high-performance liquid chromatography. Large amounts of AVP were found in the pituitary (16.3 +/- 0.56 micrograms/pituitary, n = 5) and hypothalamus (398 +/- 82.5 ng/hypothalamus), and significant amounts of AVP were also present in the cerebral cortex (26.8 +/- 11.5 ng/cortex). Plasma AVP concentrations were significantly lower (2.2 +/- 0.45 pg/ml, n = 10) during anesthesia compared to concentrations while conscious (4.5 +/- 1.19 pg/ml). Severe hemorrhage markedly increased plasma concentrations to 1091 +/- 225 pg/ml (n = 8). It was concluded that AVP is present in the possum brain, pituitary, and plasma, and that its secretion is stimulated by hypovolemia and inhibited by surgical stress.

Analysis of Variance↗

PubMed1992

Mesotocin and oxytocin in the brain and plasma of an Australian marsupial, the northern brown bandicoot, Isoodon macrourus.

1. Mesotocin (MT) and oxytocin (OT) were measured in the brain and plasma of bandicoots using reverse phase high performance liquid chromatography and specific radioimmunoassays. 2. MT and OT were found in the pituitary (1.25 +/- 0.10 micrograms/MT; 0.725 +/- 0.077 micrograms/OT) and hypothalamus (38.37 +/- 6.46 ng/MT; 19.1 +/- 4.61 ng/OT). Smaller amounts were present in the cerebral cortex. 3. Basal plasma concentrations ranged from 1.5 to 8.1 pg/ml for both peptides (N = 14) and were elevated by stress. 4. It was concluded that both MT and OT are secreted by the bandicoot brain and that stress stimulates secretion.

Animals↗

PubMed1992

The transfer of thyroxine from the mother to the young of the marsupials, the bandicoot (Isoodon macrourus) and the possum (Trichosurus vulpecula).

1. The young of the bandicoot and possum are of similar weight at birth (200-250 mg) but by day 50 post-partum have weights of 100 and 20 g, respectively. The aim of this study was to determine whether the disparate growth rate was associated with a difference in the transfer of thyroxine from mother to young. 2. Radioactive thyroxine was injected intramuscularly into the lactating female and 24 hr later a blood sample was obtained from the mother and the pouch young removed. The amount of radioactive thyroxine remaining in the blood and within the young was determined. 3. The data obtained indicated that milk is a source of thyroid hormones in early pouch life. 4. The hypothesis that greater quantities of thyroxine are transferred in the milk of bandicoots than that of brushtail possums is not supported.

Animals↗

PubMed1992

Cardiac responses after norepinephrine-induced ventricular hypertrophy in rats.

The increase in norepinephrine (NE) blood levels in human heart failure correlates with prognosis. In this study, we determined whether continuous NE infusion alters the positive inotropic and chronotropic responses of isolated rat cardiac muscles. Osmotic minipumps were implanted subcutaneously (s.c.) in 43 adult male rats to deliver NE (160 micrograms/kg/h for 14 days); 42 rats were sham-operated. Isolated left and right atria and left and right ventricular (LV, RV) papillary muscles were prepared to measure positive inotropic or chronotropic responses to NE, phenylephrine, forskolin, dibutyryl cyclicAMP (dbcyclicAMP), and calcium chloride. NE infusion caused (a) a 22% increase in LV wet weight without altering atrial or RV wet weights; (b) an 18% decrease in maximal inotropic response to calcium chloride in LV papillary muscles only; (c) a significantly decreased peak response to NE [72 +/- 5 vs. 93 +/- 5% (sham rats) of calcium chloride] but not to forskolin or dbcyclicAMP in RV papillary muscles; (d) an increased incidence of ectopy at low concentrations of NE, forskolin, and dbcyclicAMP in LV papillary muscles; (e) no alteration in papillary muscle responses to phenylephrine but significantly increased left atrial inotropic responses [51 +/- 5 vs. 33 +/- 2% (sham rats) of calcium chloride] and right atrial chronotropic responses [30 +/- 2 vs. 18 +/- 4 (sham rats) beats/min]; and (f) a selective decrease in beta 1-adrenoceptor density in both ventricles. Thus, NE infusion causes selective LV hypertrophy; responses of compounds that increase intracellular cyclicAMP are affected to a greater extent in papillary muscles from the hypertrophied ventricle than in tissues from the other chambers of the heart.

Animals↗

PubMed1992

Cardiac beta-adrenoceptor changes in experimental hyperthyroidism in dogs.

1. Triiodothyronine (T3; 1.0 mg/kg per day subcutaneously) was administered to 10 dogs for 14 days; 10 saline-treated dogs served as controls. T3-treated dogs showed the expected physiological responses of hyperthyroidism; further, chronotropic responses to isoprenaline in vivo were significantly increased in T3-treated dogs. 2. Beta-adrenoceptor subtype density was measured in membrane preparations by displacement of 125I-iodocyanopindolol binding by the selective beta 2-adrenoceptor antagonist, ICI 118, 551. T3 treatment led to a 93% increase in right atrial beta 1-adrenoceptor density and a 141% increase in left ventricular beta 1-adrenoceptor density; beta 2-adrenoceptor densities in right atrial, left ventricular and lung membranes were unchanged. 3. T3-treatment did not change basal or maximally stimulated adenylate cyclase activities in left ventricular membranes. 4. Thus, the cardiovascular changes in experimental hyperthyroidism in dogs were accompanied by an increased chronotropic response in vivo to isoprenaline and an increased beta 1-adrenoceptor density in atrial and ventricular membranes. However, there was no corresponding change in basal or maximal responsiveness of adenylate cyclase in ventricular membranes.

Adenylyl Cyclases↗