Human Atrial Natriuretic Peptide Research Articles

Plant Natriuretic Peptides are Apoplastic and Paracrine Stress Response Molecules

Higher plants contain biologically active proteins that are recognized by antibodies against human atrial natriuretic peptide (ANP). We identified and isolated two Arabidopsis thaliana immunoreactive plant natriuretic peptide (PNP)-encoding genes, AtPNP-A and AtPNP-B, which are distantly related members of the expansin superfamily and have a role in the regulation of homeostasis in abiotic and biotic stresses, and have shown that AtPNP-A modulates the effects of ABA on stomata. Arabidopsis PNP (PNP-A) is mainly expressed in leaf mesophyll cells, and in protoplast assays we demonstrate that it is secreted using AtPNP-A:green fluorescent protein (GFP) reporter constructs and flow cytometry. Transient reporter assays provide evidence that AtPNP-A expression is enhanced by heat, osmotica and salt, and that AtPNP-A itself can enhance its own expression, thereby generating a response signature diagnostic for paracrine action and potentially also autocrine effects. Expression of native AtPNP-A is enhanced by osmotica and transiently by salt. Although AtPNP-A expression is induced by salt and osmotica, ABA does not significantly modulate AtPNP-A levels nor does recombinant AtPNP-A affect reporter expression of the ABA-responsive RD29A gene. Together, these results provide experimental evidence that AtPNP-A is stress responsive, secreted into the apoplastic space and can enhance its own expression. Furthermore, our findings support the idea that AtPNP-A, together with ABA, is an important component in complex plant stress responses and that, much like in animals, peptide signaling molecules can create diverse and modular signals essential for growth, development and defense under rapidly changing environmental conditions.

Atrial natriuretic peptide is an antiapoptotic factor for human granulosa luteinized cells with impact on the results of COH/IVF in women undergoing IVF program

To investigate human granulosa luteinized cells as a local source of atrial natriuretic peptide (ANP) and its relationship to cell viability, development of preovulatory follicles and fertilization rate of oocytes. Indirect immunofluorescent technique, proANP kit, 4'6-Diamidino-2-phenylindole (DAPI)-DNA staining and Caspase-3 activity assay were used to examine localization patterns, concentrations in follicular fluids (FFl) and antiapoptotic role of ANP, respectively. ANP is expressed on granulosa cells with membrane, submembrane and specific granular cytoplasmic localization. Significant differences in the mean concentrations of ANP in FFl and in the mean levels of apoptotic human granulosa luteinized cells (GLC) were found between women with high and low immunoreactive ANP expression (P < 0.05). Concentrations of ANP correlated inversely and significantly with the percentage of apoptotic GLC isolated from the same women (r = -0.2645; P < 0.05). Enhanced in vitro production of ANP by granulosa cells (after sodium nitroproside and 2Bu-cGMP treatment), as well as after treatment with human recombinant ANP was associated with significant suppression of Caspase-3 activity compared to control cells (P < 0.05). Concentrations of ANP in FFl correlated positively and significantly with the number of punctured follicles and oocytes retrieved (r = 0.44716, r = 0.57854; P < 0.05) and with the fertilization rate of oocytes in vitro (r = 0.59773; P < 0.05). Human granulosa luteinized cells are a local source of ANP in the preovulatory human follicle, which acts as a survival factor through cGMP signaling, and its levels in follicular fluids are positively associated with the number of punctured follicles, isolated oocytes and their fertilizability in vitro.

Current biochemistry, molecular biology, and clinical relevance of natriuretic peptides

The mammalian natriuretic peptide family consists of atrial (ANP), brain [B-type; BNP] and C-type natriuretic peptide (CNP) and three receptors, natriuretic receptors-A (NPR-A), -B (NPR-B) and -C (NPR-C). Both ANP and BNP are abundantly expressed in the heart and are secreted mainly from the atria and ventricles, respectively. By contrast, CNP is mainly expressed in the central nervous system, bone and vasculature. Plasma concentrations of both ANP and BNP are elevated in patients with cardiovascular disease, though the magnitude of the increase in BNP is usually greater than the increase in ANP. This makes BNP is a clinically useful diagnostic marker for several pathophysiological conditions, including heart failure, ventricular remodeling and pulmonary hypertension, among others. Recent studies have shown that in addition to BNP-32, proBNP-108 also circulates in human plasma and that levels of both forms are increased in heart failure. Furthermore, proBNP-108 is O-glycosylated and circulates at higher levels in patients with severe heart failure. In this review we discuss recent progress in our understanding of the biochemistry, molecular biology and clinical relevance of the natriuretic peptide system.

Is Human Atrial Natriuretic Peptide (hANP) Effective as an Additive to Cardioplegic Solution During Cardiac Surgery?

Is Human Atrial Natriuretic Peptide (hANP) Effective as an Additive to Cardioplegic Solution During Cardiac Surgery?

Comparison of Nitrite Compounds and Carperitide for Initial Treatment of Acute Decompensated Heart Failure

Human atrial natriuretic peptides and nitrite compounds (NC) are infused for the initial management of acute heart failure (HF). However, there have been few studies comparing their hemodynamic effects.Fifty-two patients in acute decompensated HF (ADHF) who received carperitide (0.07 ± 0.05 µg/kg/minute, n = 23, group C) or NC (0.39 ± 0.24 µg/kg/minute, n = 29, group N) during the initial 24 hours in the intensive care unit between 1997 and 2007 were studied. We measured and compared hemodynamic parameters by pulmonary artery catheter monitoring before and after drug administration. Heart rate (HR), diastolic pulmonary artery pressure (DPAP), and central venous pressure (CVP) after the 24-hour administration were lower (HR: 92 ± 18 versus 79 ± 13 bpm, DPAP: 17 ± 6 versus 11 ± 5 mmHg, CVP: 6 ± 4 versus 3 ± 3 mmHg, P < 0.05, respectively) and the reduction of DPAP and systemic vascular resistance index were higher in group N than in group C. However, there was no significant difference regarding other indicators of preload and afterload. Although the serum B-type natriuretic peptide (BNP) level at discharge was lower in group N than group C (382 ± 434 versus 207 ± 201 pg/mL, P < 0.05), there was no significant difference in either the in-hospital reduction of BNP, the duration of hospitalization, or total cardiac events during 1-year follow-up.Although NC tended to improve the hemodynamics of ADHF more than carperitide, both drugs had a similar prognostic impact in patients with ADHF.

Low-dose Atrial Natriuretic Peptide for Chronic Kidney Disease in Coronary Surgery

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease. We investigated the effectiveness of human atrial natriuretic peptide (hANP) infusion in CKD patients undergoing coronary artery bypass grafting (CABG). We analyzed 134 consecutive cases in which CABG had been performed in our hospital from 2002 to 2005. They were divided into four groups: Group A (n = 19) was CKD + placebo, Group B (n = 30) was non-CKD + placebo, Group C (n = 22) was CKD + hANP, and Group D (n = 63) was non-CKD + hANP). The serum creatinine (mg/dl) and estimated glomerular filtration rate (ml/min/1.73 m²) were measured as evaluation values. The value of sCr changed preoperatively and at 1 year postoperatively from 1.09 ± 0.09, 51.3 ± 4.4 to 1.26 ± 0.42, 49.4 ± 14.4 in Group A, from 0.77 ± 0.14, 75.5 ± 12.1 to 0.91 ± 0.40, 72.3 ± 19.5 in Group B, from 0.99 ± 0.12, 54.8 ± 3.0 to 0.93 ± 0.16, 64.2 ± 12.3 in Group C and from 0.77 ± 0.13, 77.7 ± 13.4 to 0.83 ± 0.17, 75.9 ± 16.2 in Group D, respectively. There was a significant difference between Group A and Group C regarding the change of creatinine (p =0.0022). Our study has confirmed that an infusion of hANP during CABG in patients with CKD not only improves perioperative renal function, but also prevents the progression of CKD.

Myocardial Protective Effect of Human Atrial Natriuretic Peptide in Cardiac Surgery - "hANP Shot" in Clinical Safety Trial -

We studied low-dose human atrial natriuretic peptide (hANP) infusion therapy during cardiac surgery and reported the cardiac and renal protective effects. The efficacy of a bolus injection of hANP (the "hANP shot") simultaneously with induction of cardioplegia has been proven in animal experiments. In the present study the clinical effects of this "hANP shot" were examined. The subjects were 67 patients undergoing Coronary artery bypass grafting. At the time of inducing cardioplegia, 1 group received a simultaneous bolus injection of 100 μg of hANP (hANP group) and the other group received an injection of physiological saline (placebo group). The primary endpoints were (1) operative mortality and complications, and (2) the creatine kinase isoenzyme MB (CPK-MB), troponin-I, and human heart fatty acid binding protein (H-FABP) levels. The secondary endpoints were (1) the incidence of arrhythmia, and levels of (2) atrial and B-type natriuretic peptides, and cyclic guanosine monophosphate (cGMP), and (3) renin, angiotensin II, and aldosterone. Postoperative CPK-MB, troponin-I, and H-FABP levels were significantly lower in the hANP group than in the placebo group. Postoperative arrhythmia was significantly less frequent in the hANP group than in the placebo group. It is possible to achieve cardioprotective effects based on the safety of the "hANP shot", as well as from biomarkers of ischemia and results related to arrhythmia. The "hANP shot" should also be evaluated as a safer and new cardioprotective method for cardiac surgery.

Quantification of hormone sensitive lipase phosphorylation and colocalization with lipid droplets in murine 3T3L1 and human subcutaneous adipocytes via automated digital microscopy and high-content analysis.

Lipolysis in adipocytes is associated with phosphorylation of hormone sensitive lipase (HSL) and translocation of HSL to lipid droplets. In this study, adipocytes were cultured in a high-throughput format (96-well dishes), exposed to lipolytic agents, and then fixed and labeled for nuclei, lipid droplets, and HSL (or HSL phosphorylated on serine 660 [pHSLser660]). The cells were imaged via automated digital fluorescence microscopy, and high-content analysis (HCA) methods were used to quantify HSL phosphorylation and the degree to which HSL (or pHSLser660) colocalizes with the lipid droplets. HSL:lipid droplet colocalization was quantified through use of Pearson's correlation, Mander's M1 Colocalization, and the Tanimoto coefficient. For murine 3T3L1 adipocytes, isoproterenol, Lys-γ3-melanocyte stimulating hormone, and forskolin elicited the appearance and colocalization of pHSLser660, whereas atrial natriuretic peptide (ANP) did not. For human subcutaneous adipocytes, isoproterenol, forskolin, and ANP activated HSL phosphorylation/colocalization, but Lys-γ3-melanocyte stimulating hormone had little or no effect. Since ANP activates guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase, HSL serine 660 is likely a substrate for cGMP-dependent protein kinase in human adipocytes. For both adipocyte model systems, adipocytes with the greatest lipid content displayed the greatest lipolytic responses. The results for pHSLser660 were consistent with release of glycerol by the cells, a well-established assay of lipolysis, and the HCA methods yielded Z' values >0.50. The results illustrate several key differences between human and murine adipocytes and demonstrate advantages of utilizing HCA techniques to study lipolysis in cultured adipocytes.

Angiotensin II-stimulated secretion of arginine vasopressin is inhibited by atrial natriuretic peptide in humans

We investigated the effect of the intravenous infusion of atrial natriuretic peptide (ANP) on the response of plasma arginine vasopressin (AVP) levels to intravenous infusion of angiotensin II (ANG II) in healthy individuals. Intravenous infusion of ANP (10 ng·kg(-1)·min(-1)) slightly but significantly decreased plasma AVP levels, while intravenous infusion of ANG II (10 ng·kg(-1)·min(-1)) resulted in slightly increased plasma AVP levels. ANG II infused significant elevations in arterial blood pressure and central venous pressure (CVP). Because the elevation in blood pressure could have potentially inhibited AVP secretion via baroreceptor reflexes, the effect of ANG II on blood pressure was attenuated by the simultaneous infusion of nitroprusside. ANG II alone produced a remarkable increase in plasma AVP levels when infused with nitroprusside, whereas the simultaneous ANP intravenous infusion (10 ng·kg(-1)·min(-1)) abolished the increase in plasma AVP levels induced by ANG II when blood pressure elevation was attenuated by nitroprusside. Thus, ANG II increased AVP secretion and ANP inhibited not only basal AVP secretion but also ANG II-stimulated AVP secretion in humans. These findings support the hypothesis that circulating ANP modulates AVP secretion, in part, by antagonizing the action of circulating ANG II.

Human Atrial Natriuretic Peptide Attenuates Renal Ischemia-Reperfusion Injury

Acute kidney injury (AKI) is common in the intensive care unit, and one of its primary causes is renal ischemia-reperfusion (I/R) injury. Human atrial natriuretic peptide (hANP) exerts various pharmacologic effects, including renal protection. In the present study, we evaluated the renal protective effect of hANP in a rat model of renal I/R. Male Wistar rats were divided into three groups that received the following treatments: induction of renal I/R (I/R group); continuous intravenous injection of hANP followed 30 min later by induction of renal I/R (hANP+I/R group); and sham treatment (control group). Rats were sacrificed after 60 min of ischemia and 24 h of reperfusion or sham treatment. To evaluate the renal protective effects if hANP, serum blood urea nitrogen (BUN) and creatinine (Cre) concentrations were determined, kidneys were histologically assessed, and serum biomarkers of oxidative stress were evaluated. In addition, antimycin A (AMA)-stimulated RAW264.7 cells were treated with hANP to assess its antioxidant effects. Serum BUN and Cre levels were elevated in the I/R group; however, these increases were significantly inhibited in the hANP + I/R group. Similarly, kidney tissue damage observed in the I/R group was attenuated in the hANP + I/R group. In vitro, AMA-stimulated cells treated with hANP showed reduced reactive oxygen species activity compared to cells treated with AMA alone. Our findings indicate that hANP may be effective in the treatment of various types of I/R injuries.

Severe polyuria after the resection of adrenal pheochromocytoma

A 73-year-old male patient with hypertension and hyperglycemia was referred to our hospital because of a diagnosis regarding his left adrenal tumor. Because the levels of urinary metanephrine and normetanephrine were elevated, and (131) I-MIBG scintigraphy showed intense uptake in the adrenal tumor, the tumor was diagnosed as a pheochromocytoma. An adrenalectomy was carried out. Severe polyuria, which was accompanied by a rapid decrease in central venous pressure, started 1 hour after the operation. Urine output of more than 8000 mL/day continued until the 16th postoperative day. Plasma antidiuretic hormone (ADH) levels were within the normal range. Plasma human atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) were elevated postoperatively, and the elevation of these peptides was one possible cause for the severe polyuria. Because ADH levels in the tumor fluid were not elevated, the tumor was not an ADH-secreting tumor. Urinary β2-microglobulin was significantly elevated after the operation, thus suggesting that renal tubule dysfunction might also have been involved in the polyuria. However, the mechanism of polyuria after the resection of adrenal pheochromocytoma is not fully understood. Polyuria after the resection of adrenal pheochromocytoma is extremely rare, and the present subject is the second case to date.

Predictive Factors Associated with Left Ventricular Hypertrophy at Baseline and in the Follow‐Up Period in Non‐Diabetic Hemodialysis Patients

Hemodialysis (HD) patients frequently have an elevated left ventricular mass index (LVMI). Currently, left ventricular (LV) hypertrophy and dysfunction are considered to be the strongest predictors of cardiovascular mortality in dialysis patients. The objectives of the present study are to investigate the factors associated with elevated LVMI and to discuss therapeutic implications for the treatment strategy for pre-dialysis and HD patients. The correlation among biochemical values, physical specimens, and LVMI using echocardiography was prospectively analyzed in 30 non-diabetic HD patients in the Juntendo University Hospital. Measurement of these parameters was performed at 0, 12, and 24 months after initiation of HD. Systolic blood pressure (SP), human atrial natriuretic peptide (hANP), and hemoglobin (Hb) levels were significantly correlated with LVMI. SBP, residual glomerular filtration rate (rGFR), and serum albumin levels were identified as independent risk factors for LVMI in multivariate regression analysis at initiation of HD. SBP, hANP, and Hb levels were identified as independent risk factors for LVMI in multivariate regression analysis after 24 months. SBP, rGFR, and serum albumin levels were predictive factors for LVMI at initiation of HD. SBP, hANP, and Hb levels were also predictive factors for LVMI after initiation of HD.

Long-Term Results (Three-Year) of Emergency Coronary Artery Bypass Grafting for Patients With Unstable Angina Pectoris

Satisfactory results are achieved by elective coronary artery bypass grafting (CABG), but the results of emergency CABG are less than satisfactory and readmission for cardiac events is common. We examined long-term results of emergency CABG for unstable angina pectoris from the viewpoints of preoperative, intraoperative, and postoperative factors. Subjects were 154 patients who underwent emergency CABG for unstable angina pectoris. Operative mortality rate was 1.9%. Univariate analysis showed female gender, chronic renal failure, hemodialysis, nonuse of human atrial natriuretic peptide (hANP), nonuse of angiotensin II receptor blockers and aldosterone blockers, 3-month postoperative brain natriuretic peptide level > or =200 pg/ml, and 3-month postoperative aldosterone level > or =100 pg/ml as risk factors for late cardiac events. Multivariate analysis confirmed nonuse of hANP, nonuse of aldosterone blockers, 3-month brain natriuretic peptide level > or =200 pg/ml, and 3-month aldosterone level > or =100 pg/ml as risk factors. Intraoperative hANP infusion and postoperative treatment with aldosterone blockers and angiotensin II receptor blockers can control the renin-angiotensin-aldosterone system, inhibit left ventricular remodeling, decrease extent of infarction, and improve cardiac function, yielding a favorable long-term prognosis. The best results are obtained by combining good surgical technique and perioperative management with the long-term outcome in mind.

Atrial Natriuretic Peptide is Eliminated from the Brain by Natriuretic Peptide Receptor-C-Mediated Brain-to-Blood Efflux Transport at the Blood—Brain Barrier

Cerebral atrial natriuretic peptide (ANP), which is generated in the brain, has functions in the regulation of brain water and electrolyte balance, blood pressure and local cerebral blood flow, as well as in neuroendocrine functions. However, cerebral ANP clearance is still poorly understood. The purpose of this study was to clarify the mechanism of blood-brain barrier (BBB) efflux transport of ANP in mouse. Western blot analysis showed expression of natriuretic peptide receptor (Npr)-A and Npr-C in mouse brain capillaries. The brain efflux index (BEI) method confirmed elimination of [(125)I]human ANP (hANP) from mouse brain across the BBB. Inhibition studies suggested the involvement of Npr-C in vivo. Furthermore, rapid internalization of [(125)I]hANP by TM-BBB4 cells (an in vitro BBB model) was significantly inhibited by Npr-C inhibitors and by two different Npr-C-targeted short interfering RNAs (siRNAs). Finally, treatment with 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) significantly increased Npr-C expression in TM-BBB4 cells, as determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based targeted absolute proteomics. Our results indicate that Npr-C mediates brain-to-blood efflux transport of ANP at the mouse BBB as a pathway of cerebral ANP clearance. It seems likely that levels of natriuretic peptides in the brain are modulated by 1,25(OH)(2)D(3) through upregulation of Npr-C expression at the BBB.

Increment of monthly mean predialysis heart rate reflects early cardiac overload in hemodialysis patients with normal cardiac function

The aim of our study was to examine the association of heart rate (HR) with the onset of congestive heart failure (CHF), and to compare the predictive value of HR with that of the serum level of human atrial natriuretic peptide (hANP) and the cardiothoracic ratio (CTR). Thirty-eight patients on chronic hemodialysis (HD) aged 68 ± 11 years (61% men, 41% with diabetes) who had normal cardiac function were enrolled in this study. Among them, 6 patients had suffered CHF. Baseline characteristics and HR, hANP and CTR were compared between the 2 groups. At baseline, the monthly mean pre-HR (before HD), CTR and hANP values were higher in CHF patients compared with non-CHF patients. In the CHF group, the monthly mean pre-HR increased progressively beginning 10 months before the onset of CHF, which was earlier than the increments of hANP and CTR. A significant difference between the CHF and non-CHF groups was observed earlier for monthly mean pre-HR (4 months before CHF) and ANP (4 months before CHF) than for CTR (2 months before CHF). The increment of monthly mean pre-HR may reflect the early phase of cardiac overload, and is of equal significance to hANP. Further large-scale prospective studies are required to confirm these results.

NPR-C: a component of the natriuretic peptide family with implications in human diseases

The natriuretic peptide (NP) family includes atrial natriuretic peptide (ANP), B-type natriuretic peptide, C-type natriuretic peptide and their receptors NPR-A, NPR-B and NPR-C. The effects exerted by this hormonal system in the control of cardiovascular, renal and endocrine functions have been extensively investigated. Moreover, the involvement of NP in the pathogenesis of cardiovascular diseases has been demonstrated. Among the NP components, NPR-C has been described, at the time of its discovery, as the clearance receptor of NP devoid of any physiological functions. Emerging roles of NPR-C, however, have been highlighted over the last few years in relation to its effects on the cardiovascular system and other organs. These effects appear to be directly mediated through distinct cAMP-dependent intracellular mechanisms. Moreover, evidence has been accumulated on a potential pathophysiological role of NPR-C in human diseases. Ongoing studies from our group are revealing its involvement in the mediation of antiproliferative effects exerted on vascular cells by a molecular variant of human ANP. Thus, a new appraisal of NPR-C is overcoming the traditional view of a mere clearance receptor. This review focuses on the most important evidence supporting an involvement of NPR-C in mediating some of the actions of NP and its direct implication in cardiovascular diseases. The current state of knowledge highlights the need of further studies to better clarify the specific roles of NPR-C in pathophysiological processes.

Cardioprotection in the Clinical Setting-Lessons from J-WIND Studies

Both prevention and attenuation of ischemic heart disease are important issues, and there are three different strategies to save patients from the deleterious sequelae of ischemic injury. The first strategy is to remove the causes of ischemic heart disease; the second is to attenuate on-going ischemic and reperfusion injury; the third is to prevent the progression of cardiac remodeling and chronic heart failure following ischemic injury. For prevention of acute myocardial infarction, it is widely accepted to treat high risk patients with aspirin and/or statins. On the other hand, several medications such as angiotensin converting enzyme inhibitors, aldosterone receptor antagonists and beta blockers have been used for the prevention of post-infarction heart failure in patients who have suffered from an acute myocardial infarction. However, at present we do not have an adjunctive drug therapy to reduce infarct size in the acute phase in patients with myocardial infarction. Recently, the J-WIND trials suggested that an infusion of human atrial natriuretic peptide in the acute phase and oral administration of nicorandil in the chronic phase of infarction result in a better outcome in patients with a myocardial infarction. In this article we propose potential mechanisms for cardioprotection in patients with an acute myocardial infarction.

MOLECULAR MECHANISMS UNDERLYING THE ANTIGROWTH PROPERTIES OF THE T2238C ATRIAL NATRIURETIC PEPTIDE MOLECULAR VARIANT IN HUMAN ENDOTHELIAL CELLS IN-VITRO: PP.21.342

Objective: The CC2238 molecular variant of human atrial natriuretic peptide (ANP) significantly modulates the risk of stroke and of myocardial infarction in different populations. We recently demonstrated that CC2238 mutant ANP (mANP) inhibits endothelial cell (EC) proliferation and angiogenesis through an increased production of reactive oxygen species. The lack of cGMP stimulation excluded NPR-A and NPR-B as putative receptors mediating the effects of mANP. We currently tested the effects of mANP on EC viability and the possible involvement of NPR-C (a receptor previously implicated in the antigrowth properties of ANP) as a functional mediator of mANP. Design and Method: We stimulated EC with either regular or mANP for 12 hrs and determined cell viability by trypan blue 48 hrs later. We also measured cAMP levels in the presence of either regular or mANP. Subsequently, the effects of forskolin (10 μM), as well as of pertussis toxin, an inhibitor of Gi proteins (PTX, 50 ng/ml), were tested on cell viability during exposure of EC to mANP. The post-receptor intracellular signalling pathway was explored through the characterization of Akt and Erk1/2 phosphorylation. Results: We found that mANP significantly reduced EC viability (by 50%) and lowered cAMP levels (0.5 vs 1.0 fmol in cells treated with regular ANP). Forskolin abolished the negative effects on cell viability induced by mANP. PTX treatment was also able to recover cell viability (by 25–30%) during exposure to mANP. A significantly reduced Akt phosphorylation along with an increased ERK1/2 phosphorylation was detected in EC exposed to mANP, as compared to regular ANP. Conclusions: Our current results demonstrate that mANP induces a reduced EC viability through inhibition of adenylate cyclase and stimulation of Gi proteins. These data may support the involvement of NPR-C in the functional deleterious effects of mANP in EC. Reduced Akt phosphorylation and increased ERK1/2 activation represent the post-receptor intracellular signaling pathway. These results extend our knowledge on the fine mechanisms underlying the CC2238ANP-induced vascular damage.

Long-term effects of telmisartan on blood pressure, the renin-angiotensin-aldosterone system, and lipids in hypertensive patients

We prospectively evaluated long-term (12 months) effects of telmisartan on blood pressure (BP), circulating renin-angiotensin-aldosterone levels, and lipids in hypertensive patients. There were 13 men and 11 women, 59 +/- 8.7 years of age (mean +/- SEM), with untreated essential hypertension. The 20-60 mg doses of telmisartan were administered once daily in the morning until BP130/85 was obtained. Blood pressure and plasma renin activity, plasma angiotensin (Ang) I and Ang II, serum angiotensin-converting enzyme (ACE) activity, plasma aldosterone concentration, plasma human atrial natriuretic peptide (hANP) concentration, and serum lipids were obtained 6 and 12 months after starting telmisartan administration. Systolic and diastolic BP were significantly (P < 0.001, P < 0.001) decreased from 162 +/- 3.3 and 97.7 +/- 2.1 mmHg to 128 +/- 3.8 and 79.6 +/- 2.0 mmHg after 12 months of treatment, respectively. Plasma Ang I and Ang II were unchanged at 12 months. Plasma renin activity and serum ACE activity were significantly (P < 0.001, P < 0.05) increased and plasma aldosterone concentration was unchanged during the study period. Total cholesterol levels were unchanged, but serum triglycerides levels were significantly decreased at 12 months (P < 0.01). Plasma hANP showed no significant alteration throughout the 12-month period. In hypertensive patients, telmisartan is a beneficial antihypertensive drug that also lowers serum triglycerides.

Human Atrial Natriuretic Peptide Ameliorates LPS-Induced Acute Lung Injury in Rats

Acute lung injury, a common component of systemic inflammatory disease, is a life-threatening condition without many effective treatments. However, recent studies have demonstrated that the multifunctional human atrial natriuretic peptide (hANP) exerts anti-inflammatory effects. Therefore, we tested the hypothesis that hANP could prevent lipopolysaccharide (LPS)-induced acute lung injury in a rodent model. Rats received an LPS injection and continuous intravenous infusion (CIV) of hANP or saline solution. We evaluated the anti-inflammatory effects of hANP by histological examination and determination of serum cytokine levels and lung myeloperoxidase (MPO) activity. Histological examination revealed marked reductions in interstitial congestion, edema, inflammation, and hemorrhage in lung tissue harvested 12 h after hANP treatment compared with tissue from rats that received saline treatment after LPS. LPS injection induced elevated cytokine (IL-1beta and IL-6) secretion and lung MPO activity, which was also attenuated by hANP treatment. Taken together, these data demonstrate that hANP exerts an anti-inflammatory effect and may have potential as a therapeutic agent to treat systemic inflammatory diseases.