Biomedical subjects

M Jankowski

Publications and source records attributed to M Jankowski.

At least 19 recordsLinked to original sources

PubMed2005

Pregnancy alters nitric oxide synthase and natriuretic peptide systems in the rat left ventricle.

Cyclic guanosine monophosphate (cGMP), which is implicated in cardiac cell growth and function, is synthesized by cytoplasmic soluble guanylyl cyclase (GC) stimulated via nitric oxide (NO) and by particulate membrane-bound GC activated via natriuretic peptides. We investigated possible cGMP elevation in the left ventricle (LV) of rats developing physiologic LV hypertrophy during gestation. Furthermore, expression of estrogen receptors (ER) and oxytocin receptors (OTR) was evaluated because their activation stimulates NO and atrial natriuretic peptide (ANP) release from the heart. Compared with nonpregnant controls, Sprague-Dawley rats on day 7 of gestation had similar heart weights, but, on days 14 and 21, ventricular mass increased by 12% and 28% respectively (P< 0.05). LV cGMP concentration was elevated at day 14 of gestation (3.25 +/- 0.12 vs 4.65 +/- 0.17 pmol/g wet weight, P< 0.01) but decreased at day 21 (2.45 +/- 0.09 pmol/g, P< 0.05) to increase again on postpartum day 1 (6.01 +/- 0.15 pmol/g) and day 4 (9.21 +/- 1.79 pmol/g). Changes in endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), OTR and ERalpha, but not ERbeta, proteins paralleled the pregnancy-related cGMP changes in the LV. In contrast, ANP mRNA of the LV remained at control level throughout gestation but increased postpartum, whereas brain natriuretic peptide (BNP) expression declined at term and increased postpartum. The particulate GC natriuretic peptide receptors (GC-A and GC-B) transcripts were already lower at day 14 of gestation. Natriuretic peptide clearance receptor (NPR-C) transcript was not altered on days 7 and 14, but increased at term. We conclude that cGMP concentration in the rat LV is influenced by both NOS and natriuretic peptide systems and may be involved in the changes of LV contractility and hypertrophy that occur during rat gestation.

Animals↗

PubMed2005

Effect of cAMP analogues on glomerular inulin space of isolated rats renal glomeruli.

Cyclic AMP has been generally recognised as activator of cAMP-dependent protein kinases. However, there is little evidence about role of cAMP-dependent protein kinase (PKA), in particular izoenzymes PKA-I and PKA-II, in glomeruli contractility. We measured changes of glomerular inulin space (GIS) as a marker of its contractility in the presence of phosphodiesterase resistance cAMP analogues; activators and inhibitors of PKA. Activator of PKA i.e. (Sp) 8-Cl-cAMPS (0.1-100 microM) decreased GIS. (Rp) 8-Cl-cAMPS (0.1-100 microM), inhibitor of PKA, was ineffective but shifted concentration-response curve of (Sp) 8-Cl-cAMPS to right at 50 microM. Specific A site activation by N6-benzoyl-cAMP decreased GIS with maximum at 0.1 microM. Activation of B site by 8-aminobutyloamino-cAMP (0.1-100 microM) had no effect. However, specific activation of both sites on PKA-I or PKA-II by site-selective analogue pairs e.g. 8-aminobutyloamino-cAMP plus 8-piperidino-cAMP or N6-benzoyl-cAMP plus 8-piperidino-cAMP respectively, significantly increased sensitivity of glomeruli to analogues. Our data suggest that activation of PKA-I or PKA-II might have an important role in the regulation of glomerular contractility.

Animals↗

PubMed2005

Understanding the antiphospholipid syndrome and its treatment.

The antiphospholipid syndrome (APS) is a clinicopathologic disorder characterized by the persistent presence of anticardiolipin antibodies, lupus anticoagulants, or both in the plasma of patients with arterial or venous thrombosis or obstetric complications. The antiphospholipid antibodies involved in this syndrome have a relatively weak affinity for phospholipid-binding proteins such as b(2) glycoprotein I and prothrombin. In certain conditions they form bivalent antibody-protein complexes that bind with a relatively high affinity to negatively charged phospholipid surfaces. Evidence is accumulating for a pathogenetic role of antiphospholipid antibodies via interference with surface-mediated anticoagulant and procoagulant processes. The syndrome is characterized by the recurrence of thrombotic and obstetric complications. Retrospective studies have suggested that patients with APS and thrombosis need a high-intensity anticoagulant treatment. A few small prospective studies support treatment with a targeted INR of 2 to 3.

Antibodies, Antiphospholipid↗

PubMed2004

The cardiovascular and renal effects of the potent and highly selective mu opioid agonist [Dmt1]DALDA.

The cardiovascular and renal effects of a mu opioid agonist, [Dmt]DALDA, were studied in conscious Sprague-Dawley rats. During the first hour postinjection, [Dmt]DALDA (0.025-250 microg/rat, IV) evoked a dose-dependent diuresis. The dose of 2.5 microg increased urine volume from 1.0 +/- 0.2 to 3.4 +/- 0.3 mL/h (P < 0.001, n = 30), urinary excretion of sodium, potassium, and cGMP, and induced a mild antihypertensive effect. This dose increased cumulative 4-hour urine volume but significantly inhibited sodium and potassium excretions. The renal and cardiovascular effects were abolished by naloxone (4 mg/kg), but not by naloxonazine (35 mg/kg SC), a selective mu-1 receptor antagonist. Pretreatment with 8 mg/kg naloxone methiodide, an opioid antagonist with limited access to the brain, partially inhibited the renal effects of [Dmt]DALDA. Inhibition of nitric oxide synthases with L-NAME (1 mg/kg) had no effect on the renal and cardiovascular actions of [Dmt]DALDA. Plasma ANP and AVP, measured at 20 and 120 minutes after injection, were not altered by 2.5 and 25 microg [Dmt]DALDA. Therefore, [Dmt]DALDA evokes renal and cardiovascular effects that may primarily be mediated by central naloxonazine-insensitive mu opioid receptors (non-mu-1). These findings indicate that the central mu opioid system is involved in the regulatory mechanism of renal handling of sodium and water.

Animals↗

PubMed2004

Changes of atrial natriuretic peptide in rat supraoptic neurones during pregnancy.

To better understand the role of atrial natriuretic peptide (ANP) in the central regulation of hydro-mineral homeostasis, we analysed its expression in rat hypothalamic neurones during gestation and postpartum. These physiological events are characterized by opposing body fluid regulations. Quantitative in situ hybridization analysis showed that starting from mid-pregnancy, ANP mRNA declined in neurones of the preoptic area, periventricular area, lateral hypothalamus and endorhinal nucleus, and remained low at postpartum. By contrast, magnocellular cells in the supraoptic nucleus (SON) showed four- and 10-fold more ANP mRNA in sections from preterm and postpartum rats, respectively, compared to nonpregnant controls (P < 0.001). Oxytocin mRNA paralleled ANP mRNA expression in the SON, whereas vasopressin mRNA rose in early pregnancy and declined thereafter. High hypothalamic ANP concentration at day 21 of gestation versus nonpregnant rats (3.1 +/- 0.5 versus 1.8 +/- 0.4 ng/mg protein, P < 0.05) suggested that ANP transcript accumulation in the SON is associated with increased utilization of the peptide. The elevation of hypothalamic ANP (two-fold) and ANP receptors by treatment of ovariectomized rats with 17beta-oestradiol (25 micro g/rat, 10 days) was abolished by coadministration of progesterone. Thus, we concluded that elevated oestradiol at term stimulates ANP synthesis and paracrine ANP activation in the hypothalamus. Overall, we provide experimental, anatomical and molecular evidence for ANP regulation in hypothalamic neurones at preterm and after 17beta-oestradiol stimulation. Our study supports the concept that ANP expressed in the SON acts as a peptidergic neurotransmitter involved in water and salt regulation during pregnancy and postpartum.

Adaptation, Physiological↗

PubMed2003

Involvement of Rho-kinase in P2Y-receptor-mediated contraction of renal glomeruli.

The involvement of Rho-kinase in P2Y-receptor induced contraction of isolated rat renal glomeruli was investigated. The contraction effects have been investigated based on changes in the intracapillary volume of isolated glomeruli. ATP was found to induce time- and concentration-dependent contraction of isolated glomeruli. Other tested nucleotides (ADP, UTP) and ATP analogues (beta,gamma-methylene-ATP, 2-methylothio-ATP) contracted glomeruli in similar magnitude whereas AMP had no effect. Furthermore, the contractive effect of ATP was prevented in the presence of an antagonist of P2Y-receptors, reactive blue 2. However, a selective antagonist of A1-receptors, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), had no effect. Contraction induced by ATP, ADP, and UTP, in contrast to 2-methylothio-ATP and beta,gamma-methylene-ATP, was prevented in the presence of Rho-kinase's inhibitor, (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632). These findings suggest the involvement of Rho-kinase pathways in P2Y-induced contraction of isolated glomeruli.

Adenosine Diphosphate↗

PubMed2003

Cardiac effects of moxonidine in spontaneously hypertensive obese rats.

Moxonidine, an imidazoline receptor agonist that acts centrally to inhibit sympathetic activity, has been shown to reduce effectively blood pressure, fasting insulin levels, and free fatty acids. In this study, we investigated the long-term effects of moxonidine treatment on cardiac natriuretic peptides (ANP and BNP) in Spontaneously Hypertensive Obese Rats (SHROBs), a rat model that resembles human Syndrome X. SHROBs expressing spontaneous hypertension, insulin resistance, and genetic obesity (weight 590 +/- 20 g, at 30 weeks) received moxonidine in chow at 4 mg/kg/day for 15 days. Moxonidine significantly reduced not only systolic blood pressure (187 +/- 6 versus 156 +/- 5 mm Hg, P < 0.05) but also plasma ANP (1595 +/- 371 versus 793 +/- 131 pg/mL, P < 0.05) and BNP (22 +/- 3 versus 14 +/- 1 pg/mL, P < 0.04), without influencing cardiac content of either peptide. Semi-quantitative PCR revealed that atrial ANPmRNA/GAPDHmRNA decreased to 39% 6 10% of pair-fed controls, P < 0.03. In left ventricles, moxonidine also decreased ANP mRNA to 69% +/- 7% and BNP mRNA to 74% +/- 6% of control, P < 0.02, but right ventricular ANP and BNP mRNA were not affected. These findings indicate that chronic inhibition of sympathetic activity with moxonidine in SHROB is associated with decreased ventricular natriuretic peptide transcription, consistent with the cardioprotective effects of moxonidine given the role of ANP and BNP as markers of cadiac disease. Moxonidine also improves the metabolic profile in these rats, thus it may be considered the drug of choice in treatment of metabolic syndrome X.

Animals↗

PubMed2003

Responsiveness of renal glomeruli to adenosine in streptozotocin-induced diabetic rats dependent on hyperglycaemia level.

Glomerular filtration rate (GFR) in response to adenosine precursor, NAD, and glomeruli contractility in response to adenosine were evaluated in streptozotocin-induced diabetic rats with severe (blood glucose 27.8 +/- 1.2 mmol/L) and moderate hyperglycaemia (18.2 +/- 0.9 mmol/L) compared with nondiabetic (ND)-rats. In anaesthetised rats, basal GFR was greater in moderately diabetic rats compared with severely diabetic rats (p < 0.05) and ND-rats (p < 0.02). Intravenous infusion of 5 nmol x min(-1) x kg(-1) NAD reduced GFR and renal plasma flow (RPF) in diabetic rats but had no effect on these parameters in ND-rats. Moreover, NAD-induced reduction of GFR and RPF was greater in rats with severe diabetes (41% and 30%, respectively) than in with moderate diabetes (25% and 26%, respectively). Theophylline (0.2 micromol x min(-1) x kg(-1) ) abolished renal response to NAD. Isolated glomeruli contraction in response to adenosine, assessed by glomerular 3H-inulin space reduction, was lowered in moderately diabetic-group and enhanced in severely diabetic-group. compared with ND-group (p < 0.05). Adenosine A1-receptor antagonist DPCPX inhibited adenosine-induced glomeruli contraction. This differential response of diabetic renal glomeruli to adenosine suggests that impaired glomerular contractility in response to adenosine could be responsible for hyperfiltration in moderate diabets, whereas, the increased adenosine-dependent contractility of glomeruli in severe diabetes may increase the risk of acute renal failure in this condition.

Adenosine↗

PubMed2003

Renal haemodynamics and natriuretic responses to intravenous administration of diadenosine tetraphosphate (Ap4A) and nicotinamide adenine dinucleotide (NAD) in rat.

Effects of Ap4A and NAD--precursor of adenosine, on renal plasma flow (RPF), glomerular filtration rate (GFR) and urine excretion were determined in the anaesthetised rats. Infusion of Ap4A or NAD (i.v., bolus--1 micromol/kg followed by 10 nmol/min/kg) decreased RPF and GFR (by 30 and 40%, respectively). In spite of GFR reduction during Ap4A infusion, the significant increase in sodium excretion and urine flow was noticed: fractional sodium (FENa) and urine excretion (FEurine) rose 15-fold and 2.5-fold in comparison with the control value, respectively. In contrast to Ap4A, NAD-induced decrease in GFR was associated with parallel decrease in sodium and urine excretion, thus the FENa and FEurine did not significantly change. Pretreatment with adenosine deaminase (adenosine degrading enzyme, 2 U/min/kg) or theophylline (P1-receptors antagonist, 0.2 mmol/min/kg) ceased responses to NAD, whereas Ap4A-induced changes were not affected. Pre-treatment with suramin (P2-receptors antagonist, (i.v., bolus--12 mg/kg followed by 1.2 mg/min/kg) completely abolished the renal effects of Ap4A. We conclude that Ap4A may exert specific action on renal function. It acts different from NAD that modified renal function through its hydrolysis product--adenosine. Ap4A might reduce glomerular filtration rate and evoke natriuresis and diuresis, and its effects are probably mediated through stimulation of P2-receptors.

Animals↗

PubMed2002

Regulation of cardiac oxytocin system and natriuretic peptide during rat gestation and postpartum.

We have recently uncovered the presence of an oxytocin system in the heart and found that oxytocin is a physiological regulator of atrial natriuretic peptide (ANP), a diuretic, natriuretic and vasodilator cardiac hormone. However, dynamic changes in these systems during gestation, when mechanisms of volume and pressure homeostasis are altered, are not clear. Accordingly, ANP, oxytocin and oxytocin receptors were evaluated in rat hearts and plasma at three stages of gestation (7, 14 and 21 days) and at 2 and 5 days postpartum. Compared with non-pregnant controls, plasma ANP was elevated in mid-gestation, but significantly decreased at term (21 days), to increase again postpartum. Right and left atrial ANP mRNA levels were not altered throughout gestation but increased by 1.5- to 2-fold postpartum (P<0.01). At term, ANP content in right (8.7+/-1.2 vs 12.7+/-1.1 micro g/mg protein, P<0.04) and left (3.5+/-0.6 vs 8.5+/-2.0 micro g/mg protein, P<0.01) atria increased. These findings imply that decreased plasma ANP at term results from inhibition of release rather than decreased synthesis. In parallel, oxytocin, a stimulator of ANP release, decreased in left atria at day 7 to 50% of non-pregnant levels and remained low throughout gestation. Oxytocin receptor mRNA increased in left atria at 7 and 14 days of gestation by 2- and 5-fold respectively, but decreased at 21 days to lower than non-pregnant levels to increase again (3-fold) postpartum. The changes in oxytocin receptor expression at term and postpartum paralleled oxytocin receptor protein determined by Western blot. These results imply that pregnancy is associated with dynamic changes in the cardiac oxytocin system (peptide and/or receptors), which may influence natriuretic peptide release. Together, these peptides would act on their receptors in the heart, vasculature and kidneys to maintain vascular tone and renal function throughout gestation and postpartum.

Animals↗

PubMed2001

Estrogen receptors activate atrial natriuretic peptide in the rat heart.

In this study, semiquantitative reverse transcription-PCR analysis showed that estrogen receptor alpha (ERalpha) and beta (ERbeta) mRNAs are developmentally regulated in the rat heart. We found that ERalpha mRNA was low in all heart chambers of 4-day-old rats, but was elevated in the atria (6- to 18-fold) and ventricles (3- to 4-fold) of adult rats. Western blotting analysis confirmed that these differences were efficiently translated into 67-kDa ERalpha protein. ERbeta mRNA was expressed at its highest level in the left atrium and was 3- to 4-fold lower in other heart chambers of 4-day-old animals. In adult rats ERbeta was decreased dramatically in the left atrium (20-fold) and, to a lesser extent in the other heart chambers (2- to 4-fold). Significant ER changes occurred already in the first week after birth. Accordingly, estrogen regulation in cells from neonatal hearts, as reported in several studies, may not correspond to that occurring in fully differentiated adult hearts, because of an altered degree of ER expression. In adult rats, ovariectomy decreases atrial ERalpha, the atria/body weight ratio, and atrial natriuretic peptide (ANP) transcription. Treatment of ovariectomized rats with 17-beta-estradiol (25 microg, 10 days, s.c.) reversed these changes. In addition, there was no effect of ovariectomy and 17-beta-estradiol supplementation on systolic blood pressure, but in ovariectomized rats a decreased heart rate followed 17-beta-estradiol administration. Similar to the effects on ERalpha in the atria, ovariectomy lowered plasma ANP levels, and 17-beta-estradiol administration restored ANP in the plasma of ovariectomized rats. Changes in plasma ANP correlated with changes in ANP content in the right atrium, as demonstrated by RIA. Increased ANP expression and secretion in response to ERalpha activation may be a protective mechanism in the heart.

Animals↗

PubMed2001

Mutation A1298C of methylenetetrahydrofolate reductase: risk for early coronary disease not associated with hyperhomocysteinemia.

Diminished activity of 5,10 methylenetetrahydrofolate reductase (MTHFR), a regulatory enzyme of homocysteine metabolism, may predispose to coronary artery disease (CAD). In a case-control study we determined the prevalence of two common MTHFR polymorphisms, C677T and A1298C, in 161 male patients under the age of 50 years with angiographically documented CAD and compared it to that in 211 healthy controls. Genotyping was also performed in a random population sample, consisting of 149 men and 121 women at an average age of 40 years. The studied group had classic risk factors of atherosclerosis but did not differ in fasting plasma homocysteine, folic acid, and vitamin B12 levels in either the control group or population sample. The frequency of the 1298C allele was significantly higher in CAD (0.304) than in controls (0.199) or the population sample (0.235). Allele 1298C showed a significant association with early-onset CAD both in homozygotes and in heterozygous carriers. These findings were further supported by comparisons with the population sample. Homozygosity for allele 677T showed a tendency to associate with CAD. Allele 1298C of MTHFR is associated with early-onset CAD (carriers- RR = 1.71, 95% CI: 1.13-2.59; homozygotes- RR = 3.09, 95% CI: 1.36-7.02), even when blood homocysteine levels are not elevated.

Adolescent↗

PubMed2001

Cyclic GMP-dependent relaxation of isolated rat renal glomeruli induced by extracellular ATP.

The relaxing effect of extracellular ATP on renal glomeruli has been investigated by applying ATP and its analogues to suspensions of angiotensin II-precontracted rat renal glomeruli. Based on changes of glomerular [3H]inulin space (GIS) the relaxation of glomeruli was analysed in the presence of agonists: ATP, ADP, AMP, UTP, 2-methylthio-ATP (P2Y agonist), beta,gamma-methylene-ATP (P2X agonist) and adenosine. ATP, 2-methylthio-ATP, ADP and UTP induced concentration-dependent relaxation whereas AMP, beta,gamma-methylene-ATP and adenosine had no effect. The rank order of relaxation potency was 2-methylthio-ATP > ATP > ADP > UTP. An inhibitor of constitutive nitric oxide synthase (NOS), Nomega-nitro-L-arginine (NNA) prevented the ATP-induced increased accumulation of L-citrulline and the relaxation effect of ATP. An inhibitor of the neuronal isoform of NOS, 7-nitroindazole, had no effect on the relaxation effect of ATP. The relaxing effect of ATP was prevented in the presence of inhibitors of cyclic guanylyl cyclase: methylene blue (MB) and the more specific inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ). ATP stimulated an accumulation of cGMP that was diminished in the presence of MB. We indicated that extracellular ATP may relax the glomeruli via activation of P2Y receptors with the subsequent activation of the endothelial isoform of nitric oxide synthase and soluble guanylyl cyclase. We suggest that, based on the described mechanism, extracellular ATP may increase the filtration surface which, in turn, may influence the glomerular filtration rate.

Adenosine Triphosphate↗

PubMed2001

Anti-inflammatory effects of simvastatin in subjects with hypercholesterolemia.

AIMS: Beneficial effects of statins in preventing cardiovascular events may depend, at least in part, on their anti-inflammatory action. The aim of the study was to assess the influence of simvastatin and aspirin on serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in hypercholesterolemic subjects. METHODS AND RESULTS: In 33 asymptomatic men with total cholesterol (TC) >6.5 mmol l(-1) and in 25 men with coronary heart disease and borderline-high cholesterol levels (between 5.2 and 6.5 mmol l(-1)) chronically treated with low-dose aspirin (75 mg/d), serum levels of CRP, TNF-alpha, IL-6, and IL-8 were determined before and after a 3-month simvastatin therapy (20-40 mg daily). In the former group, these markers of inflammation were also measured before and after a 2-week treatment with aspirin (300 mg/d), implemented prior to and in combination with simvastatin. A distinct reduction of CRP and TNF-alpha was found in both groups; IL-6 levels were decreased only in subjects with marked hypercholesterolemia. Aspirin had no effect on the anti-inflammatory action of simvastatin. CONCLUSIONS: In men with hypercholesterolemia simvastatin treatment lowers serum levels of CRP and proinflammatory cytokines. Low-dose aspirin does not add to the anti-inflammatory action of simvastatin.

Adult↗

PubMed2001

The opossum kidney cell type IIa Na/P(i) cotransporter is a phosphoprotein.

BACKGROUND/AIM: Parathyroid hormone (PTH)-dependent inhibition of proximal tubular P(i) reabsorption is mediated by protein kinase A and/or C and is associated with reduced border membrane expression of the type IIa Na/P(i) cotransporter. The aim of this study was to analyze phosphorylation of the type IIa cotransporter protein. METHODS: Opossum kidney cells were used as a 'proximal tubular' cell model. Protein phosphorylation was determined by immunoprecipitation of the type IIa Na/P(i) cotransporter, followed by autoradiography. The transporter protein content was evaluated by Western blotting and transport activity by tracer P(i) uptake. RESULTS: Under control conditions (no PTH) the transporter was phosphorylated; upon treatment with PTH, a decrease in phosphorylation was observed. A protein phosphatase inhibitor (okadaic acid) was unable to prevent PTH-induced Na/P(i) cotransporter inhibition but reduced transporter degradation. CONCLUSION: The type IIa Na/P(i) cotransporter is a phosphoprotein, but alterations in its phosphorylation seem not to be involved in P(i) transport inhibition.

Animals↗

PubMed2001

Chromosomal and comparative mapping of rat oxytocin, oxytocin receptor and vasopressin genes.

Oxytocin and its receptor are potentially important for cardiovascular functions. In the present paper, we report their chromosome locations in the rat and their comparative mapping with the mouse and human. They are located in chromosome regions previously known to contain quantitative trait loci for blood pressure in various genetic crosses. Thus, they have become valid candidate genes for genetic hypertension.

Animals↗

PubMed2000

Oxytocin and its receptors are synthesized in the rat vasculature.

Produced and released by the heart, oxytocin (OT) acts on its cardiac receptors to decrease the cardiac rate and force of contraction. We hypothesized that it might also be produced in the vasculature and regulate vascular tone. Consequently, we prepared acid extracts of the pulmonary artery and vena cava of female rats. OT concentrations in dog and sheep aortae were equivalent to those of rat aorta (2745 +/- 180 pg/mg protein), indicating that it is present in the vasculature of several mammalian species. Reverse-phase HPLC of aorta and vena cava extracts revealed a single peak corresponding to the amidated OT nonapeptide. Reverse-transcribed PCR confirmed OT synthesis in these tissues. Using the selective OT receptor ligand compound VI, we detected a high number of OT-binding sites in the rat vena cava and aorta. Furthermore, OT receptor (OTR) mRNA was found in the vena cava, pulmonary vein, and pulmonary artery with lower levels in the aorta, suggesting vessel-specific OTR distribution. The abundance of OTR mRNA in the vena cava and pulmonary vein was associated with high atrial natriuretic peptide mRNA. In addition, we have demonstrated that diethylstilbestrol treatment of immature female rats increased OT significantly in the vena cava but not in the aorta and augmented OTR mRNA in both the aorta (4-fold) and vena cava (2-fold), implying regulation by estrogen. Altogether, these data suggest that the vasculature contains an intrinsic OT system, which may be involved in the regulation of vascular tone as well as vascular regrowth and remodeling.

Animals↗

PubMed2000

Corticotropin-releasing hormone causes antidiuresis and antinatriuresis by stimulating vasopressin and inhibiting atrial natriuretic peptide release in male rats.

In both normally hydrated and volume-expanded rats, there was a biphasic effect of corticotropin-releasing hormone (CRH) (1-10 microgram, i.v.) on renal function. Within the first hour, CRH caused antidiuresis, antinatriuresis, and antikaliuresis together with reduction in urinary cGMP output that, in the fourth hour, were replaced by diuresis, natriuresis, and kaliuresis accompanied by increased cGMP output. Plasma arginine vasopressin (AVP) concentrations increased significantly within 5 min, reached a peak at 15 min, and declined by 30 min to still-elevated values maintained for 180 min. Changes in plasma atrial natriuretic peptide (ANP) were the mirror image of those of AVP. Plasma ANP levels were correlated with decreased ANP in the left ventricle at 30 min and increased ANP mRNA in the right atrium at 180 min. All urinary changes were reversed by a potent AVP type 2 receptor (V(2)R) antagonist. Control 0.9% NaCl injections evoked an immediate increase in blood pressure and heart rate measured by telemetry within 3-5 min. This elevation of blood pressure was markedly inhibited by CRH (5 microgram). We hypothesize that the effects are mediated by rapid, direct vasodilation induced by CRH that decreases baroreceptor input to the brain stem, leading to a rapid release of AVP that induces the antidiuresis by direct action on the V(2)Rs in the kidney. Simultaneously, acting on V(2)Rs in the heart, AVP inhibits ANP release and synthesis, resulting in a decrease in renal cGMP output that is responsible for the antinatriuretic and antikaliuretic effects.

Animals↗