Hyperbranched polyglycerol electrospun nanofibers for wound dressing applications.

This study reports on the performance of electrospun hyperbranched polyglycerol nanofibers capable of providing an active agent delivery for wound dressing applications. The aim of this work was to prepare electrospun HPGL nanofibers containing Calendula officinalis as a wound-healing and anti-inflammatory agent. The morphology of the electrospun HPGL-C. officinalis nanofibers was analyzed using a scanning electron microscope. The results showed that the diameters of the fibers were in nanoscales. The release of C. officinalis from the electrospun HPGL fibers was determined by HPLC at a physiological temperature (37 degrees C). Rapid release of the C. officinalis from the electrospun HPGL-C. officinalis nanofibers was exhibited as result of the high swelling ability as well as the high porosity of the electrospun HPGL-C. officinalis membranes. The degree of swelling, and the mechanical and biocompatible properties of the electrospun HPGL fibers were determined. The results showed that, in physiological conditions, the water absorption into the HPGL electrospun fibers slowed down, governed by the rate at which the electrospun HPGL-C. officinalis membranes interacted with the physiological fluid. The rate of release of C. officinalis seemed to depend on the C. officinalis content in the HPGL nanofibers. From the elastic modulus, it could be seen that elastic electrospun HPGL fibers were obtained with increments of C. officinalis content in the HPGL-C. officinalis membranes. The results of in vivo experiments in rats suggested that HPGL-C. officinalis might be an interesting bioactive wound dressing material for clinical applications.

Effect of selective angiotensin antagonists on the antidiuresis produced by angiotensin-(1-7) in water-loaded rats

In the present study we evaluated the nature of angiotensin receptors involved in the antidiuretic effect of angiotensin-(1-7) (Ang-(1-7)) in water-loaded rats. Water diuresis was induced in male Wistar rats weighing 280 to 320 g by water load (5 ml/100 g body weight by gavage). Immediately after water load the rats were treated subcutaneously with (doses are per 100 g body weight): 1) vehicle (0.05 ml 0.9 percenr NaCl); 2) graded doses of 20, 40 or 80 pmol Ang-(1-7); 3) 200 nmol Losartan; 4) 200 nmol Losartan combined with 40 pmol Ang-(1-7); 5) 1.1 or 4.4 nmol A-779; 6) 1.1 nmol A-779 combined with graded doses of 20, 40 or 80 pmol Ang-(1-7); 7) 4.4 nmol A-779 combined with graded doses of 20, 40 or 80 pmol Ang-(1-7); 8) 95 nmol CGP 42112A, or 9) 95 nmol CGP 42112A combined with 40 pmol Ang-(1-7). The antidiuretic effect of Ang-(1-7) was associated with an increase in urinary Na+ concentration, an increase in urinary osmolality and a reduction in creatinine clearance (CCr: 0.65 ñ 0.04 ml/min vs 1.45 ñ 0.18 ml/min in vehicle-treated rats, P<0.05). A-779 and Losartan completely blocked the effect of Ang-(1-7) on water diuresis (2.93 ñ 0.34 ml/60 min and 3.39 ñ 0.58 ml/60 min, respectively). CGP 42112A, at the dose used, did not modify the antidiuretic effect of Ang-(1-7). The blockade produced by Losartan was associated with an increase in CCr and with an increase in sodium and water excretion as compared with Ang-(1-7)-treated rats. When Ang-(1-7) was combined with A-779 there was an increase in CCr and natriuresis and a reduction in urine osmolality compared with rats treated with Ang-(1-7) alone. The observation that both A-779, which does not bind to AT1 receptors, and Losartan blocked the effect of Ang-(1-7) suggests that the kidney effects of Ang-(1-7) are mediated by a non-AT1 angiotensin receptor that is recognized by Losartan.

Diuresis and natriuresis produced by long term administration of a selective Angiotensin-(1-7) antagonist in normotensive and hypertensive rats.

In this study we evaluated the renal effects of chronic administration of the selective Angiotensin-(1-7)[Ang-(1-7)] antagonist, A-779, in normotensive and spontaneously hypertensive rats (SHR). Male adult SHR and Wistar rats were housed in metabolic cages with tap water and standard chow, for three-five days before starting infusion (Alzet osmotic mini-pumps) of A-779 (Wistar: 1 microg/h, n = 9; 2.5 microg/h, n = 6; SHR:2.5 microg/h, n = 6) or vehicle (0.9% NaCl - 1 microl/h, n = 7 and n = 10 for SHR and Wistar rats, respectively). Urine volume, water and food intake and urinary Na+ were measured daily. On the last day of infusions mean arterial pressure (MAP) was recorded and urine and blood samples were collected to determine renal function parameters. Chronic infusion of A-779 produced a sustained increase in diuresis in normotensive rats [seventh day values: 0.75+/-0.08 ml/h (1 microg/h) and 0.94+/-0.13 ml/h (2.5 microg/h) vs. 0.42 + 0.03 ml/h for the control group, P<0.05] associated to a dose-dependent increase in the creatinine clearance. In SHR, diuresis increased significantly after chronic infusion of A-779 (fifth day values: 0.44 + 0.06 ml/h vs. 0.25+/-0.04 ml/h for the control group, P<0.05), without changes in creatinine clearance. Infusion of A-779 in normotensive rats produced a decrease in water reabsorption. A-779 infusion also produced a dose-dependent increase in urinary Na+ excretion (1.49 + 0.14 mEq, 1 microg/h vs. 2.37+/-0.22 mEq, 2.5 microg/h, P<0.05), in Wistar rats, without modifying the fractional excretion of Na+. In SHR, urinary Na+ excretion was also increased by A-779 (2.21+/-0.46 mEq vs. 0.94+/-0.22 mEq for the control group, P<0.05). No significant changes in blood pressure were observed. These findings suggest that endogenous Ang-(l-7) participates in the control of hydroelectrolyte balance by modulating water excretion, acting at tubular and glomerular sites.

Effect of selective angiotensin antagonists on the antidiuresis produced by angiotensin-(1-7) in water-loaded rats.

In the present study we evaluated the nature of angiotensin receptors involved in the antidiuretic effect of angiotensin-(1-7) (Ang-(1-7)) in water-loaded rats. Water diuresis was induced in male Wistar rats weighing 280 to 320 g by water load (5 ml/100 g body weight by gavage). Immediately after water load the rats were treated subcutaneously with (doses are per 100 g body weight): 1) vehicle (0.05 ml 0.9% NaCl); 2) graded doses of 20, 40 or 80 pmol Ang-(1-7); 3) 200 nmol Losartan; 4) 200 nmol Losartan combined with 40 pmol Ang-(1-7); 5) 1.1 or 4.4 nmol A-779; 6) 1.1 nmol A-779 combined with graded doses of 20, 40 or 80 pmol Ang-(1-7); 7) 4.4 nmol A-779 combined with graded doses of 20, 40 or 80 pmol Ang-(1-7); 8) 95 nmol CGP 42112A, or 9) 95 nmol CGP 42112A combined with 40 pmol Ang-(1-7). The antidiuretic effect of Ang-(1-7) was associated with an increase in urinary Na+ concentration, an increase in urinary osmolality and a reduction in creatinine clearance (CCr: 0.65 +/- 0.04 ml/min vs 1.45 +/- 0.18 ml/min in vehicle-treated rats, P < 0.05). A-779 and Losartan completely blocked the effect of Ang-(1-7) on water diuresis (2.93 +/- 0.34 ml/60 min and 3.39 +/- 0.58 ml/60 min, respectively). CGP 42112A, at the dose used, did not modify the antidiuretic effect of Ang-(1-7). The blockade produced by Losartan was associated with an increase in CCr and with an increase in sodium and water excretion as compared with Ang-(1-7)-treated rats. When Ang-(1-7) was combined with A-779 there was an increase in CCr and natriuresis and a reduction in urine osmolality compared with rats treated with Ang-(1-7) alone. The observation that both A-779, which does not bind to AT1 receptors, and Losartan blocked the effect of Ang-(1-7) suggests that the kidney effects of Ang-(1-7) are mediated by a non-AT1 angiotensin receptor that is recognized by Losartan.

Renal actions of angiotensin-(1-7).

The heptapeptide angiotensin-(1-7) is considered to be a biologically active endproduct of the renin-angiotensin system. This angiotensin, which is devoid of the most known actions of angiotensin II such as induction of drinking behavior and vasoconstriction, has several selective effects in the brain and periphery. In the present article we briefly review recent evidence for a physiological role of angiotensin-(1-7) in the control of hydroelectrolyte balance.

Renal actions of angiotensin-(1-7)

The heptapeptide angiotensin-(1-7) is considered to be a biologically active endproduct of the renin-angiotensin system. This angiotensin, which is devoid of the most known actions of angioatensin II such as induction of drinking behavior and vasoconstriction, has several selective effects in the brain and periphery. In the present article we briefly review recent evidence for a physiological role of angiotensin-(1-7) in the control of hydroelectrolyte balance.

Evidence for a physiological role of angiotensin-(1-7) in the control of hydroelectrolyte balance.

In this study we evaluated the possibility that angiotensin-(1-7) [Ang-(1-7)] acts as an endogenous osmoregulatory peptide by determining the effect of acute administration of its selective antagonist [D-Ala7]Ang-(1-7) (A-779) on renal function parameters in rats. In addition, we investigated the physiological mechanisms involved in the antidiuretic effect of Ang-(1-7). The antidiuretic effect of Ang-(1-7) (40 pmol/0.05 mL per 100 g BW) in water-loaded rats was completely blocked by A-779 (vehicle-treated, 3.34 +/- 0.43 mL/h; Ang-(1-7), 1.48 +/- 0.23; A-779, 2.72 +/- 0.35; Ang-(1-7) plus A-779, 3.26 +/- 0.49). In contrast, the antidiuretic effect of Ang-(1-7) was not significantly changed by a vasopressin V2 receptor antagonist in a dose that completely blocked the antidiuresis produced by an equipotent dose of vasopressin. In addition, Ang-(1-7) administration did not significantly change vasopressin plasma levels in water-loaded rats. The antidiuretic effect of Ang-(1-7) in water-loaded rats was associated with a reduction of creatinine clearance (0.68 +/- 0.04 versus 1.38 +/- 0.32 mL/min in vehicle-treated rats, P <.05) and an increase in urine osmolality (266.8 +/- 32.7 versus 182.8 +/- 14 mOsm/kg in vehicle-treated rats, P <.05). An effect of Ang-(1-7) in tubular water transport was demonstrated in vitro by a fourfold increase in the hydraulic conductivity of inner medullary collecting ducts in the presence of 1 nmol/L Ang-(1-7). Subcutaneous administration of A-779 (2.3 to 9.2 nmol/100 g) produced a significant increase in urine volume (4.6 nmol/100 g, 0.45 +/- 0.12 mL/h; vehicle-treated rats, 0.16 +/- 0.03 mL/h; P <.05) comparable to that of acute administration of a vasopressin V2 receptor antagonist. The diuretic effect of A-779 was associated with an increase in creatinine clearance and decrease in urine osmolality. In contrast, no significant effects on urine volume were observed after systemic administration of angiotensin subtype 1 or 2 receptor antagonists (DuP 753 and CGP 42112A, respectively). These findings suggest that endogenous Ang-(1-7), acting on specific receptors, participates in the control of hydroelectrolyte balance by influencing especially water excretion.

Characterization of a new angiotensin antagonist selective for angiotensin-(1-7): evidence that the actions of angiotensin-(1-7) are mediated by specific angiotensin receptors.

In this study we describe a new angiotensin antagonist [Asp1-Arg2-Val3-Tyr4-Ile5-His6-D-Ala7, (A-779)] selective for the heptapeptide angiotensin-(1-7) [Ang-(1-7)]. A-779 blocked the antidiuretic effect of Ang-(1-7) in water-loaded rats and the changes in blood pressure produced by Ang-(1-7) microinjection into the dorsal-medial and ventrolateral medulla. In contrast, A-779 did not change the dipsogenic, pressor, or myotropic effects of angiotensin II (Ang II). Also, A-779 did not affect the antidiuretic effect of vasopressin or the contractile effects of angiotensin III, bradykinin, or substance P on the rat ileum. In the rostral ventrolateral medulla, the pressor effect produced by Ang-(1-7) microinjection was completely blocked by A-779 but not by AT1 or AT2 receptor antagonists (DUP 753 and CGP 42112A, respectively). Conversely, the pressor effect produced by Ang II was not changed by A-779 but was completely blocked by DUP 753. Binding studies substantiated these observations: A-779 did not compete significantly for 125I-Ang II binding to adrenocortical membranes at up to a 1 microM concentration. Low affinity binding was also observed in adrenomedullary membranes with an IC50 greater than 10 microM. Our results show that A-779 is a potent and selective antagonist for Ang-(1-7). More importantly, our data indicate that specific angiotensin receptors mediate the central and peripheral actions of Ang-(1-7).

Angiotensin-(1-7) is a potent antidiuretic peptide in rats.

We have shown previously that angiotensin-(1-7) (Asp-Arg-Val-Tyr-Ile-His-Pro) is a biologically active endogenous angiotensin which is a major product of angiotensin I processing by an angiotensin converting enzyme (ACE)-independent pathway. Intense staining for angiotensin-(1-7) immunoreactivity was demonstrable in brain areas related to the maintenance of hydromineral balance, suggesting the involvement of this peptide in this process. In the present study we investigated the antidiuretic effect of angiotensin-(1-7) by determining its effect on the water diuresis produced by an ip water load (5 ml/100 g) in male Wistar rats. The peptide had a pronounced antidiuretic effect when administered peripherally in doses ranging from 5.5 to 22 pmol/100 g. In contrast, angiotensin II presented only a small effect with the highest dose used (20 pmol/100 g). Comparison of the potency of angiotensin-(1-7) and vasopressin (AVP) showed that both peptides act in the same molar range although AVP was slightly more potent than angiotensin-(1-7). Urine volumes for 22 pmol/100 g angiotensin-(1-7) were 0.85 +/- 0.26 and 3.47 +/- 0.36 ml for hours 1 and 2, respectively, whereas they were 0.54 +/- 0.40 and 2.38 +/- 0.64 ml for 10 pmol/100 g AVP. There was apparent additivity of effect when 10 pmol of each peptide were administered simultaneously (0.0 and 1.72 +/- 0.45 ml vs 2.58 +/- 0.45 and 3.85 +/- 0.35 ml for control for hours 1 and 2, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-1(1-7) is a potent antidiuretic peptide in rats

We have shown previously that angiotensin (1-7) (Asp-Arg Val-Tyr-Ile-His-Pro) is a biologically active endogenous angiotensin which is a major product of angiotensin I processing by an angiotensin converting enzyme (ACE)-independent pathway. Intense staining for angiotensin (1-7) immunoreactivity was demonstrable in brain areas related to the maintenance of hydromineral balance, suggesting the involvement of this peptide in this process. In the present study we investigated the antidiuretic effect of angiotensin (1-7), by determining its effect on the water diuresis produced by an ip water load (5 ml/100 g) in male Wistar rats. The peptide had a pronounced antidiuretic effect when administered peripherally in doses ranging from 5.5 to 22 pmol/100 g. In contrast, angiotensin - (1-7) and vasopressin (AVP) showed that both peptides act in the same molar range althouth AVP was slightly more potent than angiotensin (1-7). Urine volumes for 22 pmol/100 g angiotensin (1-7) were 0.85 ñ 0.26 and 3.47 ñ 0.36 ml for hours 1 and 2, respectively, whereas they were 0.54 ñ 0.40 and 2.38 ñ 0.64 ml for 10 pmol/100 g AVP. There was apparent additivity of effect when 10 pmol of each peptide were administered simultaneously (0.0 and 1.72 ñ 0.45 ml vs 2.58 ñ 0.45 and 3.85 ñ 0.35 ml for hours 1 and 2, respectively). The unexpected potency of this peptide in reducing water diuresis and its localization in brain areas related to AVP release suggest a role for angiotensin (1-7) in the mechanisms involved in the maintenance of hydroelectrolyte balance