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Biomedical subjects

I Tikkanen

Publications and source records attributed to I Tikkanen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of temperature of insufflated CO2 during and after prolonged laparoscopic surgery.

BACKGROUND: Pneumoperitoneum with room temperature carbon dioxide (CO2) has been shown to decrease core temperature and urine output. METHODS: The effect of 37 degrees C (warm) and room temperature (cool) CO2 pneumoperitoneum on core temperature, urine output, and central hemodynamics was compared in 26 randomized patients undergoing prolonged laparoscopic surgery (>90 min). RESULTS: The core temperature (p < 0.05) and cardiac index (p < 0.05) were significantly higher after warm than after cool pneumoperitoneum. Urine output was significantly higher during warm (2.3 +/- 1.6 ml/kg/h) than during cool (0.9 +/- 0.7 ml/kg/h) insufflation (p < 0. 05). Two of 13 patients with warm and 11 of 13 patients with cool pneumoperitoneum needed mannitol to maintain adequate diuresis (p < 0.05). CONCLUSIONS: Warm insufflation probably causes a local vasodilation in the kidneys and may be beneficial to patients with borderline renal function.

Body Temperature↗
PubMed1998

Effect of oxygen on pulmonary hemodynamics and incidence of atrial fibrillation after noncardiac thoracotomy.

OBJECTIVE: The mechanism of postthoracotomy atrial fibrillation (AF) could be related to right ventricular (RV) strain. The effect of oxygen on the occurrence of postoperative AF and on RV function was studied. DESIGN: A prospective, randomized study. SETTING: A university hospital. PARTICIPANTS: Twenty-four noncardiac thoracotomy patients. INTERVENTIONS: At the end of the postoperative anesthesia care unit period, the patients were randomly allocated to receive 35% oxygen until either the third (P = prolonged group) or the first postoperative morning (S = short group). MEASUREMENTS AND MAIN RESULTS: Measurement of hemodynamic variables using a thermodilution pulmonary artery catheter, oxygenation, concentration of plasma atrial natriuretic peptide (ANP) and Holter monitoring were started preoperatively and continued for the 3 postoperative days (PODs). Systolic RV pressure (systolic RVP) and pulmonary vascular resistance (PVR) increased postoperatively only in group S. Major changes in RV performance were not seen with echocardiography or the thermodilution method in any patient. Silent episodes of AF occurred in three patients (25%) in group P and in one patient (8%) in group S (not significant [NS]) without deviations in plasma ANP concentration. On each of the 3 PODs, all patients were exposed to 60% oxygen for 15 minutes. Systolic RVP decreased significantly during the exposure to 60% oxygen only in group S, but not in patients developing AF. Predictive factors for AF were a high preoperative PVR, intraoperative bleeding necessitating volume loading, and elevated systolic RVP immediately after thoracotomy. CONCLUSION: Short episodes of AF occurred irrespective of the length of oxygen therapy. Occurrence of AF could not be explained by changes in RV function.

Atrial Fibrillation↗
PubMed1998

A comparison of gasless mechanical and conventional carbon dioxide pneumoperitoneum methods for laparoscopic cholecystectomy.

UNLABELLED: Carbon dioxide (CO2) insufflation with increased intraabdominal pressure (IAP) has adverse hemodynamic, pulmonary, and renal effects. To avoid these problems, an abdominal wall lift method with a retractor was used to provide the surgical view without CO2 insufflation. Twenty-six patients undergoing elective laparoscopic cholecystectomy were randomly allocated to either the gasless, retractor group, or conventional CO2 pneumoperitoneum group (CPP). Hemodynamic data, ventilatory variables, urine output, urine oxygen tension, and blood samples for determining stress hormones were collected throughout the perioperative period. Patients in the retractor group had lower mean arterial pressure, heart rate, and central venous pressure (P < 0.001). They also had higher pulmonary dynamic compliance and needed a lower minute volume of ventilation to achieve normocarbia (P < 0.001). Urine output and oxygen tension in urine were higher (P < 0.05) with the retractor method than with CPP. Increase in plasma renin activity (P < 0.05) and decrease in core temperature (P < 0.001) were smaller with the gasless method than with CPP. The gasless method for laparoscopic cholecystectomy might be beneficial, especially in patients with compromised cardiorespiratory or renal function. IMPLICATIONS: Totally gasless laparoscopic cholecystectomy was compared with conventional pressure pneumoperitoneum with CO2 insufflation. The gasless method resulted in more stable hemodynamics and pulmonary function, as well as higher urine, output than conventional pressure pneumoperitoneum. No changes in renal oxygenation was seen with the gasless method, compared with conventional pressure pneumoperitoneum.

Adult↗
PubMed1998

Screening for renovascular hypertension in a population with relatively low prevalence.

OBJECTIVE: To evaluate the accuracy and cost-efficacy of the diagnostic procedure and treatment for renovascular hypertension. SETTING AND PATIENTS: A total of 519 patients referred to the university clinic for hypertension were screened for renovascular hypertension with 405 captopril challenge tests (CCT) and 450 captopril renographies (CRG). INTERVENTIONS: Abdominal angiography was performed on 84 patients for positive screening. Fifteen patients underwent angiography for a sole suspicious clinical presentation. The angiography revealed 17 renal artery stenoses and five occlusions in 20 patients. Fifteen technically successful angioplasties and three nephrectomies were performed. RESULTS: In the patients who underwent angiography, CCT had a specificity of 39% and a sensitivity of 67% for renovascular hypertension. CRG had a sensitivity of 100% and a specificity of 68%. In the whole study population, the estimated specificity of CCT was 88% and that of CRG 95%. Invasive treatment reduced systolic/diastolic blood pressure from 157/99 to 140/87 mmHg and the number of antihypertensive drugs used from 2.6 to 1.4 in 16 patients (mean age 49 years). Angiotensin converting enzyme (ACE) inhibition was effective in four elderly patients. Cost-efficacy analysis Screening with CRG and invasive treatment cost US$15400 per successful invasive treatment Equally effective pharmacological treatment would have cost US$10400. Limiting the screening with CRG to the 173 patients with no obvious renal parenchymal disease and with hypertension at a younger age (< or =30 years) or unresponsive to two antihypertensive drugs (diastolic blood pressure > 90 mmHg) would have yielded a prevalence of 12% and missed only one elderly patient who responded to ACE inhibition. The limited screening, along with invasive treatment, would have cost US$7300 per patient CONCLUSIONS: CRG is superior to CCT for screening of renovascular hypertension. Screening with CRG is cost-effective when limited to patients with no obvious renal parenchymal disease and with hypertension that does not respond to two antihypertensive drugs or is detected in patients no older than 30 years.

Adolescent↗
PubMed1998

Effects of esmolol on haemodynamic response to CO2 pneumoperitoneum for laparoscopic surgery.

BACKGROUND: Carbon dioxide (CO2) pneumoperitoneum for laparoscopic surgery increases arterial pressures, systemic vascular resistance and heart rate and decreases urine output. METHODS: In this double-blind randomized study esmolol, an ultrashort-acting beta1-adrenoceptor antagonist was compared with physiological saline (control) in 28 patients undergoing laparoscopic surgery in standardized 1 MAC isoflurane anaesthesia. Alfentanil infusion was used to prevent the increase of mean arterial pressure more than 25% from baseline. RESULTS: Esmolol effectively prevented the pressor response to induction and maintenance of CO2 pneumoperitoneum. Significantly (P<0.001) less alfentanil was needed in the esmolol group than in the control group. Urine output was higher (P<0.05) and plasma renin activity (P<0.01) and urine N-acetyl-beta-D-glucosaminidase levels lower in the esmolol group when compared with the control group. CONCLUSIONS: Esmolol blunts the pressor response to induction and maintenance of pneumoperitoneum and may protect against renal ischaemia during pneumoperitoneum.

Acetylglucosaminidase↗
PubMed1998

Dual inhibition of neutral endopeptidase and angiotensin-converting enzyme in rats with hypertension and diabetes mellitus.

It has been suggested that combined inhibition of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) may lower blood pressure more effectively than either treatment alone, independent of the degree of salt and volume status or the activity of the renin-angiotensin system. The effects of NEP inhibition in hypertension associated with diabetes mellitus are largely unknown. We therefore compared ACE inhibition, NEP inhibition, and dual NEP/ACE inhibition in diabetic hypertensive rats. Spontaneously hypertensive rats (SHR) aged 9 to 10 weeks were injected with either streptozotocin (45 mg/kg) or citrate buffer and randomized to receive either the ACE inhibitor captopril (25 mg/kg BID), the NEP inhibitor SCH 42495 (30 mg/kg BID), the dual NEP/ACE inhibitor S 21402 (25 or 50 mg/kg BID), or vehicle by gavage for 4 weeks. A group of diabetic SHR was also allocated to receive the combination of SCH 42495 (30 mg/kg BID) and captopril (25 mg/kg BID). The degree of renal NEP inhibition was determined by autoradiography, and plasma renin activity (PRA) was determined by radioimmunoassay. In diabetic SHR, the dual NEP/ACE inhibitor (50 mg/kg BID), as well as the combination of the NEP inhibitor and the ACE inhibitor, reduced systolic blood pressure more effectively than the ACE inhibitor (P<0.001) or the NEP inhibitor (P<0.001) alone. In nondiabetic SHR, the dual NEP/ACE inhibitor and the ACE inhibitor were equally effective, while the NEP inhibitor had only slight blood pressure lowering effects. Relative heart weight decreased in parallel to the changes in blood pressure. Renal NEP was clearly inhibited (70% to 92%; P<0.001) by both the NEP inhibitor and the dual NEP/ACE inhibitor. Both the ACE inhibitor and the dual NEP/ACE inhibitor increased PRA, but the stimulating effect of dual NEP/ACE inhibition on PRA was less than that observed with ACE inhibition alone (P<0.05). Albuminuria in diabetic SHR was lower during treatment with both the dual NEP/ACE inhibitor (50 mg/kg BID) and the combination of NEP inhibition and ACE inhibition compared with vehicle treatment (P<0.05). In conclusion, the present study shows that hypertension in SHR with streptozotocin-induced diabetes is modulated by natriuretic peptides and thus is sensitive to NEP inhibition. The increased efficacy of dual NEP/ACE inhibition on blood pressure in diabetic SHR, compared with ACE or NEP inhibition alone, suggests that this therapeutic approach may prove beneficial in the treatment of hypertension associated with diabetes mellitus and other forms of volume-dependent hypertension.

Analysis of Variance↗
PubMed1998

Mechanism of progression of renal disease: current hemodynamic concepts.

BACKGROUND: Hypertension, a known independent risk factor for end-stage renal failure, damages the kidney in multiple ways. It produces hemodynamic and mechanical stress, which may lead to glomerular endothelial dysfunction. Both of these mechanisms may lead to increased glomerular leakiness, hence proteinuria, which may damage the kidney further. Hypertension may also stimulate the production of vasoactive substances that, in turn, activate the production of cytokines and growth factors, leading to the production of extracellular matrix proteins. Thus, the progression of renal failure is related to both systemic and glomerular hemodynamic changes and to the activation of vasoactive hormones, growth factors and cytokines. THERAPY: To protect the kidney, we need to control or prevent the occurrence of these factors. Therapy with effective antihypertensive agents, such as angiotensin-converting enzyme inhibitors, has been shown to slow the progression of end-stage renal disease.

Animals↗
PubMed1997

Associations between atrial natriuretic peptides, echocardiographic findings and mortality in an elderly population sample.

OBJECTIVES: To examine associations of N-terminal and C-terminal components of the proatrial natriuretic peptide [ANP (1-98) and ANP (99-126), respectively], with echocardiographic measurements of left ventricular structure and performance and with the function of the aortic and mitral valves in old age. To compare the predictive value of the atrial peptides and echocardiographic data for short-term mortality. DESIGN: A population based survey with 1.5-year mortality follow-up. SETTING: University hospital. SUBJECTS: Three-hundred and thirty-three people aged 78-88 years. MAIN OUTCOME MEASURES: (i) Plasma ANP (1-98) and ANP (99-126); (ii) M-mode and Doppler echocardiographic measurements of left atrial diameter; left ventricular diameters, mass and fractional shortening; peak transmitral velocities; aortic valve area, aortic regurgitation jet length and mitral regurgitant jet area; (iii) total and cardiovascular 1.5-year mortality. RESULTS: ANP (1-98) correlated with left atrial diameter (r = 0.33; P < 0.001), left ventricular mass (r = 0.19; P < 0.001), fractional shortening (r = -0.16; P < 0.01) and the early-to-atrial peak transmitral velocity ratio (r = 0.23; P < 0.001). Also, ANP (1-98) predicted the degree of aortic valve obstruction and the severity of aortic and mitral regurgitation. Associations of ANP (99-126) with echocardiographic data were much weaker. Aortic valve stenosis and ANP (1-98) were independent predictors of age- and sex-adjusted total and cardiovascular mortality at 1.5 years of entry. CONCLUSIONS: Circulating ANP (1-98) correlates with left atrial size, with left ventricular mass and performance and with the severity of aortic and mitral valve dysfunction in persons representing the general elderly population. ANP (1-98) also predicts both total and cardiovascular mortality.

Aged↗
PubMed1997

Delayed increase in blood pressure induced by spontaneously hypertensive rat plasma after high sodium intake.

Plasma from spontaneously hypertensive rats (SHR) and from patients with essential hypertension has been suggested to contain a substance with a delayed pressor effect, parathyroid hypertensive factor (PHF), associated with salt-sensitive forms of hypertension. In order to study whether high sodium intake would increase plasma levels of PHF-like activity, determined by bioassay, SHR received either a high-sodium (2.6% Na in the chow) or a normal-sodium (0.3% Na) diet for 6 weeks. Intravenous injection of plasma from SHR on a high-sodium diet (6 ml/kg) to urethane-anaesthetized Wistar rats induced a delayed increase in mean arterial blood pressure 70-80 min after bolus injection. No delayed pressor effects could be demonstrated by plasma from SHR or Wistar rats on a normal-sodium diet. It is concluded that a factor with a delayed blood pressure-increasing effect appears to be present in plasma from SHR on a high-sodium diet but not in plasma from normotensive Wistar rats or SHR on a normal-sodium diet. Further studies to characterize this factor and its possible relation to salt-induced hypertension are warranted.

Animals↗
PubMed1997

Endothelin-1 in heart and pulmonary tissue in experimental heart failure.

We studied the effect of congestive heart failure (CHF) on the tissue levels of endothelin 1 (ET-1) and of the mRNA of prepro-ET-1 in the rat. Congestive heart failure was produced by ligation of the left coronary artery. The rats were killed 3 weeks after the ligation. Congestive heart failure was determined by elevated plasma atrial natriuretic peptide and by a myocardial infarction scar covering more than 30% of the left ventricular circumference. Both ET-1 and prepro-ET-1 mRNA were measured in cardiac ventricles and lungs by radioimmunoassay and quantitative polymerase chain reaction. The rats with CHF had an increased heart weight/body weight ratio and elevated plasma atrial natriuretic peptide levels. In rats with CHF, as compared to controls, the concentration of ET-1 was elevated 3.6-fold in pulmonary tissue and 1.4-fold in the right ventricle, respectively, but not in the left ventricle. The concentration of mRNA showed a similar pattern, but due to methodological limitations this was assumed to represent a rough estimate only. The enhanced production of ET-1 in the right ventricle and in the pulmonary tissue may be of pathophysiological importance for the development of high pulmonary vascular resistance in CHF.

Animals↗
PubMed1997

Comparison of renin-angiotensin to calcium channel blockade in renal disease.

Whether any class of antihypertensive drugs has specific renoprotective effects above and beyond lowering of blood pressure is still debatable. The renin-angiotensin system (RAS) is both localized and has many actions within the kidney, on intrarenal hemodynamics, on the mesangial cell, as well as stimulating growth factors and cytokines. Angiotensin converting enzyme (ACE) inhibitors have been shown to ameliorate the progression of renal failure. How much of this beneficial effect is due to their hemodynamic effects, how much to non-hemodynamic effects and how much to their effects on bradykinin and other putative ACE substrates is still unclear. Experimentally it can be shown that inhibiting ACE but preventing the fall in systemic blood pressure by salt loading abolishes renoprotection. Bradykinin has been implicated in both the beneficial and the adverse effects of ACE inhibitors. Because of this and because ACE inhibitors may not provide complete blockade of the RAS, angiotensin receptor (AT1R) antagonists have been developed. Experimentally AT1R antagonists have been shown to reproduce most of the beneficial effects of ACE inhibitors. The experience in humans is more limited but they have been demonstrated to be efficacious in hypertension, to reduce proteinuria, and produce a favorable hemodynamic effect in congestive cardiac failure with a low incidence of adverse effects and without cough. Calcium channel blockers (CCB) also have additional properties that may provide renoprotection beyond lowering blood pressure. However, as the different types of CCB block different calcium channels their effects may differ substantially. The inconsistency of the data in the renoprotective effect of CCB may reflect these differences. Quantitatively probably the most important factor in preventing the progress of renal failure by antihypertensive drugs is strict control of blood pressure. Lowering blood pressure by drugs is most likely effective by both reducing physical and sheer stress damage, as well as turning off the signal for the activation and production of vasoactive peptides and cytokines.

Angiotensin II↗
PubMed1996

Randomized comparison of the neuroendocrine response to laparoscopic cholecystectomy using either conventional or abdominal wall lift techniques.

Increase in plasma renin activity and noradrenaline concentration occur in response to carbon dioxide insufflation during laparoscopic cholecystectomy. In a randomized study the conventional carbon dioxide pneumoperitoneum was compared with the abdominal wall lift method for laparoscopic cholecystectomy, with special reference to neuroendocrine changes and renal function. The total mean(s.d.) volume of carbon dioxide insufflated was 42(23) litres with the conventional method and 9(7) litres with abdominal wall lift (P < 0.001). Mean(s.d.) intra-abdominal pressure after 15 min of insufflation was 11(2) and 3(9) mmHg respectively (P < 0.01). In the conventional group mean(s.d.) plasma renin activity increased slightly from 5.5(2.1) to 6.1(2.0) ng ml-1 during the first 55 min of laparoscopic cholecystectomy. In the abdominal wall lift group plasma renin activity decreased from 5.3(2.7) to 3.8(0.9) ng ml (P < 0.01 between the groups). Plasma antidiuretic hormone concentration increased similarly in both groups. Diuresis was significantly less with conventional pneumoperitoneum during the first 35 min of the operation compared with the abdominal wall lift method (P < 0.001). There were significant increases in plasma noradrenaline concentration in both groups (P < 0.001), but the increase was slightly higher in the conventional group during the first 15 min of insufflation. The abdominal wall lift method with minimal carbon dioxide insufflation was associated with smaller neuroendocrine responses and better preservation of renal function compared with conventional carbon dioxide pneumoperitoneum.

Adult↗
PubMed1996

Increased serum neutral endopeptidase activity in acute renal allograft rejection.

Neutral endopeptidase (EC 3.4.24.11; NEP), originally isolated from renal tubular brush border, is a cell surface peptidase identical to the CD10 antigen (or CALLA; common acute lymphoblastic leukemia antigen) in lymphoid cells. We studied the serum NEP levels daily after transplantation (Tx) in 19 renal allograft recipients. The NEP activity was determined with a two-step enzymatic assay utilizing a fluorogenic substrate (Suc-Ala-Ala-Phe-AMC; see text) and related to clinical signs of graft rejection, to signs of immunoactivation in transplant fine-needle aspiration biopsy (FNAB) specimens, to renal function, and to serum levels of C-reactive protein. The serum NEP levels remained normal (peak level 10.3 +/- 1.8 micrograms/l on days 6-9 after Tx, initial level after Tx 7.3 +/- 1.4 micrograms/1 on day 2; mean values +/- SEM) in patients who neither showed clinical signs of rejection nor had findings of immunoactivation in FNAB samples. On the contrary, the serum NEP levels rose clearly in patients developing acute rejection verified clinically and in FNAB samples (peak value 90.4 +/- 18.7 micrograms/l on days 6-9 post-Tx; p < 0.001 compared with patients without sings of immunoactivation) and even in patients having immunoactivation in FNAB without clinical evidence of rejection (108.2 +/- 22.4 micrograms/l, p < 0.001). Serum NEP peak appeared 2-3 days before clinical diagnosis of rejection and a positive findings in FNAB samples. Serum NEP increments did not correlate with changes in serum creatinine, delayed onset of renal excretory function, blood leukocyte count, C-reactive protein level, or infections. Thus, the serum NEP activity was shown to increase after renal allotransplantation associated with early phases of immunoactivation and development of acute graft rejection. Because of the limited number of patients studied, the clinical implications of these preliminary observations for kidney transplant monitoring clearly need confirmation in larger studies.

Adolescent↗
PubMed1996

Chronic inhibition of nitric oxide synthase in Heymann nephritis.

Effects of nitric oxide (NO) synthase inhibition on blood pressure and on the course of Heymann nephritis was examined in rats. L-NG-nitroarginine-methylester (L-NAME, 10 mg/100 ml in the drinking water for 12 weeks) was used as an inhibitor of NO synthase. Urinary excretion of guanosine 3',5'-cyclic monophosphate (cGMP), a second messenger of NO, was used as an indirect estimate of NO activity. Rats were divided into the following groups: control, nephritis, L-NAME, and nephritis-L-NAME. Urinary cGMP excretion was lower in the nephritis group (p < 0.05) and in the nephritis-L-NAME group (p < 0.005) compared with controls. Plasma atrial natriuretic peptide (ANP) levels were elevated in the nephritis (p < 0.001) and in the nephritis-L-NAME groups (p < 0.05. L-NAME treatment alone did not have any effect on plasma ANP levels. Blood pressure rose progressively in all L-NAME-treated rats. Most marked albuminuria developed in the nephritis-L-NAME group. No differences in the immunohistological findings were observed between the nephritis and the nephritis-L-NAME groups. NO synthase inhibition causes hypertension and aggravates albuminuria in chronic nephritis. Moreover, nephritis itself may decrease then production of cGMP either as a consequence of blunted NO activity or, in addition, because of ANP resistance. It appears that NO synthase inhibition does not change the immunological course of Heymann nephritis but rather the increased hemodynamic load makes the course of nephritis worse.

Albuminuria↗
PubMed1996

Polymorphism of the glycogen synthase gene in hypertensive and normotensive subjects.

Hypertension and non-insulin-dependent diabetes mellitus (NIDDM) are characterized by a strong genetic component and impaired ability to store glucose as glycogen in skeletal muscle. Impaired insulin activation and altered genetic control of muscle glycogen synthase, the rate-limiting enzyme for glucose storage in skeletal muscle, could provide an explanation for this insulin resistance. We examined whether there is an association between the glycogen synthase gene (Xba I polymorphism) and hypertension in 304 nondiabetic subjects. We examined glucose tolerance with an oral glucose tolerance test and glucose storage in skeletal muscle with the euglycemic insulin clamp technique in combination with indirect calorimetry. The Xba I A2 allele of the glycogen synthase gene was enriched in subjects with hypertension and a family history of NIDDM (48%) compared with normotensive subjects without a family history of NIDDM (6%, P < .0001). The presence of the A2 versus the A1 allele was associated with decreased rates of insulin-stimulated glucose storage in hypertensive subjects (11.2 +/- 2.3 versus 16.9 +/- 2.6 mumol/kg lean body mass per minute, P = .029) but not in normotensive subjects (28.0 +/- 4.6 versus 29.6 +/- 3.7 mumol/kg lean body mass per minute). In conclusion, Xba I polymorphism of the glycogen synthase gene identifies a subgroup of hypertensive subjects with a family history of NIDDM. The data suggest that a locus in the glycogen synthase gene region on chromosome 19 may serve as a "thrifty gene," increasing susceptibility for insulin resistance when exposed to other environmental or genetic factors.

Adult↗
PubMed1995

Increased renal expression of cytokines and growth factors induced by DOCA-NaCl treatment in Heymann nephritis.

DOCA-NaCl treatment causes hypertension, accelerates development of proteinuria, and leads to glomerulosclerosis in rats with autoimmune Heymann nephritis. To study the mechanisms of kidney injury induced by renal haemodynamic load in chronic nephritis, we studied by immunohistochemistry the local expression of various cytokines, growth factors and adhesion molecules in the kidneys of Heymann nephritic rats with or without DOCA-NaCl-induced hypertension. The DOCA-NaCl-nephritis group developed hypertension and marked renal enlargement as compared with the nephritis group, the DOCA-NaCl group, and the controls. Albuminuria appeared earlier and was heavier in the DOCA-NaCl-nephritis group compared with the nephritic rats without DOCA-NaCl. Expression of IL-6, TNF-alpha, GM-CSF, b-FGF, NGF, TGF-beta, and ICAM-1 was enhanced in the kidneys of the DOCA-NaCl-nephritis group as compared with other groups, localized mainly in the glomerular mesangium (IL-6, GM-CSF, TGF-beta), glomerular and peritubular endothelium (ICAM-1), and collecting ducts (TNF-alpha, b-FGF, NGF, TGF-beta), possibly associated with the observed tubulointerstitial mononuclear cellular infiltration. Thus in autoimmune Heymann nephritis, DOCA-NaCl treatment causes hypertension and increased renal mass together with upregulation of local cytokine and growth factor production, which may further aggravate hypertension and accelerate progression of renal damage.

Animals↗
PubMed1995

Comparison of the angiotensin II antagonist losartan with the angiotensin converting enzyme inhibitor enalapril in patients with essential hypertension.

OBJECTIVE: To evaluate the blood pressure lowering efficacy as well as tolerability and safety of the angiotensin II antagonist losartan compared with that of the angiotensin converting enzyme inhibitor enalapril in patients with mild-to-moderate essential hypertension. DESIGN AND METHODS: The study was a multicentre, double-blind, double-dummy, randomized, parallel study. Patients (n = 407) with diastolic blood pressure > or = 95 and < or = 120 mmHg at the end of a 2-week baseline placebo period were randomly allocated to receive either 50 mg losartan once a day or 20 mg enalapril once a day for 12 weeks. Blood pressure, clinical and laboratory safety, specific symptoms including coughing determined using a symptoms questionnaire and metabolic variables were examined at baseline and at weeks 6 and 12. RESULTS: Both losartan and enalapril decreased systolic and diastolic blood pressure from baseline at weeks 6 and 12. Blood pressure changes from baseline at trough (22-26 h after the dose) did not differ between the two groups in the per-protocol analysis. Response to treatment at trough was excellent or good (diastolic blood pressure < 90 mmHg or reduction in diastolic blood pressure of 10 mmHg) in 51 and 53% of the patients in the losartan and enalapril groups, respectively. Enalapril administration increased dry coughing symptoms whereas losartan did not. The incidence of dry coughing was 1.0 and 12.2% as a spontaneously reported discomfort at week 12 and 3.0 and 15.1% as a clinical adverse experience in the losartan and enalapril groups, respectively. The difference from baseline at week 12 in the incidence of dry coughing between the two groups was 14.9% as a specific symptom in the symptoms questionnaire. Losartan reduced serum uric acid concentration, whereas effects on other metabolic parameters did not differ between the groups. CONCLUSIONS: Losartan is an effective and well-tolerated antihypertensive drug showing similar blood-pressure-lowering efficacy to that of enalapril at trough. However, in contrast to enalapril, losartan does not increase the incidence of dry coughing. Thus, the angiotensin II antagonist losartan provides a promising new approach to treatment of hypertension.

Adult↗