Antioxidant and antihypertensive activity of extract from Thymus serpyllum L. in experimental hypertension.

The low incidence of cardiovascular disease in Mediterranean countries leads to an increased interest of the scientific community for the Mediterranean diet. Our aim was to evaluate total phenol and flavonoid contents, antioxidant capacity, free radical scavenging activity and potential antihypertensive effect of aqueous extract obtained from Thymus serpyllum L. (wild thyme, TE), an aromatic herb from the Lamiaceae family (highly present in Mediterranean diet), in spontaneously hypertensive rats (SHR) and in normotensive Wistar rats. Total phenol content of TE was 2008.33 ± 10.6 mg/L GAE, and rosmarinic and caffeic acids were predominant phenolic compounds. The ferric reducing/antioxidant power and antioxidant capacity analysis revealed strong antioxidative properties of TE. In vitro nitric oxide-scavenging activity of 1 mg/l TE was 63.43% with the IC50 value of 122.36 µg/ml. Bolus injection of TE (100 mg/kg body weight i.v.) induced significant decrease of systolic and diastolic blood pressure and total peripheral resistance in SHR, without effects on these parameters in normotensive Wistar rats. Cardiac index remained unchanged after TE treatment in all experimental rats. Given dose of TE did not show significant nitric oxide-scavenging activity in vivo. Our results indicate that TE may protect against hypertension in experimental model of essential hypertension.

Prevention of systemic and regional haemodynamic alterations, hypercreatininemia, hyperuremia and hyperphosphatemia by losartan in hypertension with acute renal failure.

Patients with pre-existing hypertension are at a particular risk of fatal outcome due to acute renal failure (ARF). We investigate the effects of angiotensin II type-1 receptor blocker (ARB) losartan, on haemodynamics and biochemical parameters in adult male spontaneously hypertensive rats (SHR) with ischemia/reperfusion ARF. SHR were randomly selected in three experimental groups: sham-operated group (SHAM), ARF group, and ARF+LOS group (losartan, 10 mg/kg/b.w. given by infusion during the period of three hours after reperfusion). Beside the improvement of systemic haemodynamics 24 h after reperfusion, losartan significantly increased renal blood flow (RBF: 19.33±3.29 ml/min/kg vs. 8.03±1.04 ml/min/kg, p<0.05) and decreased renal vascular resistance (RVR) compared to ARF (8.85±1.21 mmHg × min × kg/ml vs. 19.90±2.35 mmHg × min × kg/ml, p<0.001). Plasma creatinine (Pcr), urea (Pu) and phosphates (Pphos) were significantly reduced in ARF+LOS group compared to ARF group (Pcr: 99.11±14.56 µmol/l vs. 242.71±20.25 µmol/l, p<0.001; Pu: 33.72±4.69 mmol/l vs. 61.90±3.93 mmol/l, p<0.001; 2.7±0.42 mmol/l vs. 5.57±0.61 mmol/l, p<0.01). Our results demonstrate that losartan improves systemic and regional haemodynamic and biochemical parameters in hypertension with ARF.

The effects of iron-containing superoxide dismutases on haemodynamic parameters in spontaneously hypertensive rats.

The product of FeSOD activity is hydrogen peroxide (H2O2). Furthermore, FeSOD can modify the chemical versatility of NO into its redox-active forms: nitrosonium cation (NO+) and nitroxyl anion (NO-). All of these low molecular weight species are vasoactive and, in particular, NO- induces calcitonin gene-related peptide (CGRP) synthesis (known to be the most potent relaxation-promoting peptide). In this study the effects of bolus infusions of iron-containing superoxide dismutase (FeSOD) and of superoxide dismutase containing both iron and manganese (FeMnSOD) on the arterial blood pressure (MAP), the arterial blood pressure (CO) and the total vascular resistance (TVR) in spontaneously hypertensive (SH) rats were determined. Bolus infusion of FeSOD induced a biphasic response in the MAP (an initial increase was followed by a significant decrease). At the end of the experiment the MAP returned to its basal value. FeMnSOD (the enzymatically inactive form of FeSOD) had no effect on the MAP in these experiments. Bolus infusions of FeSOD and of FeMnSOD had no effect either on the both the CO or on the TVR in SH rats. Our results indicate that arterial relaxation changes mediated by NO- may be important for regulation of blood pressure in SH rats.

Influence of carvedilol on chronic renal failure progression in spontaneously hypertensive rats with adriamycin nephropathy.

BACKGROUND: In this study, the effects of carvedilol, antihypertensive (alpha-beta blocker) agent with antiproliferative and antioxidative properties, on slowing down of chronic renal failure (CRF) progression in spontaneously hypertensive rats (SHR) with adriamycin (ADR) nephropathy were examined. METHODS: Eighty adult (24 weeks) SHR were divided into four groups: CONTROL GROUP: 20 SHR; ADR group: 20 SHR treated with ADR (2 mg/kg i.v. twice in 20 days); ADR-C group: 20 SHR treated with ADR and with carvedilol (30 mg/kg/day); ADR-CC group: 20 SHR treated with carvedilol and captopril (60 mg/kg/day). Systolic blood pressure was measured every two weeks, renal blood flow (RBF), mean arterial pressure (MAP) and renal vascular resistance (RVR) were determined at Weeks 6 and 12, creatinine clearance and proteinuria at Weeks -3 (see measurements), 6 and 12. The rats were sacrificed at Weeks 6 and 12 after the second ADR injection. Glomerular sclerosis, tubulointerstitial and blood vessel changes were determined by semiquantitative scoring. RESULTS: Carvedilol decreased systolic blood pressure. It decreased RVR and MAP, and increased RBF significantly. Carvedilol also significantly decreased interstitial infiltration in the early phase of the study, slowed down the development of interstitial fibrosis and tubular atrophy and decreased blood vessel changes. The hemodynamic and morphological effects of carvedilol were associated with slowing down the CRF progression as well as a mild decrease in proteinuria. Captopril addition to carvedilol improved its effects especially on prevention of tubulointerstitial changes. CONCLUSIONS: Results of this experimental study showed beneficial effect of carvedilol and its combination with captopril on CRF progression, indicating that clinical studies are warranted.

L-arginine reduces tubular cell injury in acute post-ischaemic renal failure.

BACKGROUND: The pathophysiology of renal ischaemia, resulting in tubular cell injury and leading to acute renal failure (ARF), remains unclear. An ever-increasing number of investigations focus on a possible role of nitric oxide (NO) in regulating circulation during ARF. In this context, we investigated the influence of chronic stimulation or inhibition of NO synthesis, or both, on haemodynamic parameters, histology and plasma renin activity (PRA) after ischaemia-reperfusion injury of rat kidneys. METHODS: Experiments were performed on adult, male Wistar rats. Before induction of ARF, a group of animals was treated with a NO synthesis inhibitor (L-NAME) and another group was treated with a precursor of NO synthesis (L-arginine). The animals received those substances for 4 weeks. Control groups received the same amount of tap water for 4 or 8 weeks and were divided into groups with ARF (4 weeks--ARF group and 8 weeks ARF group) and a sham-operated group. Another group of rats was treated first with L-NAME and then with L-arginine in their drinking water, for 4 weeks for each of these two substances. All parameters were evaluated 24 h after the induction of ischaemic ARF or the sham operation. RESULTS: Our results show that such long-term stimulation of NO release by L-arginine improved renal haemodynamics in the ischaemic form of ARF. Renal blood flow (RBF) increased by 96% in the L-arginine-treated rats with ARF compared with the group with ARF alone. Inhibition of NO synthesis worsens renal haemodynamics after ARF. However, this aggravation can be reversed by L-arginine. The rate of water reabsorption was reduced in all groups with ARF, but this reduction was least in the group treated with L-arginine. The rate of Na+ reabsorption was reduced in all groups 24 h after renal ischaemia, but a significant decrease was observed after the inhibition of NO synthesis. Histological examination of the kidney specimens showed that morphological changes were least in the rats treated with L-arginine, when compared with all other groups with ARF. Nevertheless, the lesions were most prominent in the L-NAME+ARF group. In this group, the areas of corticomedullar necrosis were more widespread in comparison with other groups, especially the L-arginine group where only swelling of the proximal tubular cells was observed. Treatment with L-NAME was not accompanied by any significant alteration in the plasma concentration of angiotensin I (ANG I), while in the group treated with L-arginine ANG I had a tendency to decrease. CONCLUSIONS: Acute post-ischaemic renal failure may be alleviated by administering the NO substrate (L-arginine). NO acts cytoprotectively on tubular epithelial cells in ischaemia--reperfusion injury of rat kidney. Evidence of this comes from both histopathological findings and increased tubular water and sodium reabsorption. However, inhibition of NO synthesis (provoked by L-NAME) worsens renal haemodynamics and aggravates morphological changes after ARF. These aggravations can, however, be reversed by L-arginine.