Glomerular and tubular effects of nitric oxide (NO) are regulated by angiotensin II (Ang II) in an age-dependent manner through activation of both angiotensin receptors (AT1Rs and AT2Rs) in conscious lambs.

Renin-angiotensin (RAS) and nitric oxide (NO) systems and the balance and interaction between them are considered of primary importance in maintaining fluid and electrolyte homeostasis. It has been suggested that the effects of NO may be modulated at least in part by the angiotensin (Ang) II, yet the roles of angiotensin receptor type 1 (AT1R) and type 2 (AT2R) are not well understood. Even though both Ang II and NO are elevated at birth and during the newborn period, their contribution to the adaptation of the newborn to life after birth as well as their physiological roles during development are poorly understood.

Renal effects of angiotensin II in the newborn period: role of type 1 and type 2 receptors.

Background: Evidence suggests a critical role for the renin-angiotensin system in regulating renal function during postnatal development. However, the physiological relevance of a highly elevated renin-angiotensin system early in life is not well understood, nor which angiotensin receptors might be involved. This study was designed to investigate the roles of angiotensin receptors type 1 (AT1R) and type 2 (AT2R) in regulating glomerular and tubular function during postnatal development.

Developmentally regulated effects of severe hemorrhage on cardiovascular homeostasis and the arterial baroreflex control of heart rate.

The purpose of this study was to investigate in developing animals, the cardiovascular responses to severe hemorrhage at which compensatory mechanisms fail and when blood pressure remains decreased after blood loss. Two groups of conscious lambs (Group I: one to two weeks, N = 7; group II: six to seven weeks, N = 7) were studied. Mean arterial pressure, systolic and diastolic pressures, and heart rate were measured for 20 min before (Control, C) and for 60 min after a fixed hemorrhage of 30% of blood volume.

Angiotensin type 1 and type 2 receptors during ontogeny: cardiovascular and renal effects.

The renin-angiotensin system (RAS) is a major component of cardiovascular and renal homeostasis, maintaining blood pressure and water and electrolyte balance in health and disease. Whilst knowledge regarding the RAS in adult organisms has substantially increased over the last three decades, physiological effects and levels of functioning of the system during the perinatal period are poorly understood. It has been shown, however, that the RAS is subject to remarkable developmental changes that involve all system components, including the main active biologic peptide, angiotensin II (Ang II) and the receptors through which these effects are mediated, type 1 receptors (AT1Rs) and type 2 receptors (AT2Rs).

Angiotensin receptors modulate the renal hemodynamic effects of nitric oxide in conscious newborn lambs.

This study aimed to elucidate the roles of both angiotensin II (ANG II) receptors - type 1 (AT1Rs) and type 2 (AT2Rs) - separately and together in influencing hemodynamic effects of endogenously produced nitric oxide (NO) during postnatal development. In conscious, chronically instrumented lambs aged ~1 week (8 ± 1 days, N = 8) and ~6 weeks (41 ± 2 days, N = 8), systolic, diastolic, and mean arterial pressure (SAP, DAP, MAP) and venous pressure (MVP), renal blood flow (RBF), and renal vascular resistance (RVR) were measured in response to the l-arginine analog, l-NAME after pretreatment with either the AT1R antagonist, ZD 7155, the AT2R antagonist, PD 123319, or both antagonists. The increase in SAP, DAP, and MAP by l-NAME was not altered by either ATR antagonist in either age group.

Do angiotensin type 2 receptors modulate haemodynamic effects of type 1 receptors in conscious newborn lambs?

Introduction And Hypothesis: It was hypothesized that in the immediate newborn period, when the renin-angiotensin system (RAS) is activated, angiotensin type 2 receptors (AT2Rs) buffer the haemodynamic effects of angiotensin type 1 receptors (AT1Rs), as occurs in adult animals when the RAS is activated.

Materials And Methods: Arterial (systolic, diastolic, and mean) pressures (SAP, DAP, MAP), mean venous pressures (MVP) and renal blood flows (RBF) were measured in conscious, chronically instrumented lambs aged ~1 (8±2 days, N=8) and 6 weeks (41±4 days, N=11). In each animal, measurements were made before and after administration of the selective AT1R antagonist ZD 7155 (experiment one) and the selective AT2R antagonist PD123319 (experiment two) as well as both antagonists, ZD 7155 and PD 123319 (experiment three).

Cyclooxygenase (COX) Inhibitors and the Newborn Kidney.

This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI) in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2) plays a more important role in during fetal development and influences kidney function early in life is not known, though evidence points to a predominant role for COX-2.

Haemodynamic responses to angiotensin II in conscious lambs: role of nitric oxide and prostaglandins.

It was hypothesized that nitric oxide (NO) and prostaglandins (PGs) play a synergistic role in modulating haemodynamic responses to angiotensin II (ANG II) in an age-dependent manner. To this end, experiments were carried out in conscious, chronically instrumented lambs aged ∼1 week (N = 9) and ∼6 weeks (N = 10) to evaluate the haemodynamic responses to ANG II, before and after treatment with the L: -arginine analogue, N-nitro-L: -arginine methyl ester (L: -NAME), as well as the cyclooxygenase inhibitor, indomethacin (INDO). Pressor and renal blood flow responses to ANG II were measured before (control) and after administration of L: -NAME (20 mg kg(-1)), following pretreatment with either vehicle (VEH) (experiment 1) or INDO (1 mg kg(-1), experiment 2).

Nitric oxide and angiotensin II regulate cardiovascular homeostasis and the arterial baroreflex control of heart rate in conscious lambs.

To investigate the potential role of angiotensin II (Ang II) type 1 receptors (AT(1)Rs) as well as endogenously produced nitric oxide (NO) in regulating cardiovascular homeostasis during ontogeny, experiments were carried out in conscious lambs aged approximately 1 week (N = 9) and 6 weeks (N = 11). The arterial baroreflex control of heart rate (HR) was assessed before and after intravenous (IV) infusion of the selective AT(1)R antagonist, ZD 7155, before and after IV administration of the L-arginine analogue, N(G)-nitro-L-arginine methyl ester (L-NAME). In both groups, after ZD 7155 alone, mean arterial pressure decreased then increased after L-NAME.

Indomethacin abolishes core temperature, but not cardiovascular or renal, responses to lipopolysaccharide in conscious lambs.

1. Core temperature (Tc), cardiovascular and renal responses to lipopolysaccharide (LPS), as well as the role of endogenously produced prostaglandins (PG) in influencing these responses, were investigated in the present study in conscious, chronically instrumented lambs. 2.

Do prostaglandins modulate renal haemodynamic effects of endothelin-1 in conscious lambs?

To test the hypothesis that vasodilatory prostaglandins buffer the renal vasoconstrictor effects of endothelin-1 (ET-1) early in life, renal haemodynamic responses to ET-1 were measured in 2 groups of conscious, chronically instrumented lambs at 1-2 weeks of age (group I, n = 11) and 6 weeks of age (group II, n = 10). Lambs were pretreated with vehicle or 1 mg x kg(-1) indomethacin, a nonselective cyclooxygenase inhibitor, and renal haemodynamic effects were measured continuously for 1 min before (control) and 5 min after intra-arterial injection of 250 ng x kg(-1) ET-1. In group II lambs, there was a marked decrease in renal blood flow (RBF) and renal vascular conductance (RVC) elicited by ET-1 administration, as we have previously described.

Kappa opioids modulate the arterial baroreflex control of heart rate in conscious young sheep.

The present study tested the hypothesis that kappa-opioids modulate the arterial baroreflex control of heart rate in conscious young sheep. Various parameters governing the arterial baroreflex control of heart rate were assessed before and after activation of kappa-opiate receptors (KOR) by i.v.

Renal responses to the kappa-opioid-receptor agonist U-50488H in conscious lambs.

In adult animals and humans, activation of kappa-opioid receptors results in a diuresis. The aim of the present study was to investigate whether kappa-opioids are also diuretic early in life and whether this is altered during postnatal maturation. Therefore, the renal effects of the kappa-opioid-receptor agonist U-50488H were measured in two separate age groups of conscious lambs at two stages of postnatal maturation (approximately 1 wk and approximately 6 wk) under physiological conditions.

Effects of indomethacin on systemic and renal haemodynamics in conscious lambs.

Both prostaglandins (PGs) PGE(2) and PGI(2) can act as renal vasodilators, these effects being exacerbated when the renin-angiotensin system is activated. Therefore, we hypothesized that PGs would play a more predominant role in modulating renal haemodynamics in the newborn period, when the renin-angiotensin system is activated. To this end, the role of endogenously produced PGs in modulating systemic and renal haemodynamics was investigated in two groups of conscious lambs aged approximately 1 and approximately 6 weeks.

Systemic and renal hemodynamic effects of the AT1 receptor antagonist, ZD 7155, and the AT2 receptor antagonist, PD 123319, in conscious lambs.

Experiments were carried out to investigate age- and dose-dependent effects of the selective AT(1) receptor antagonist, ZD 7155, and the selective AT(2) receptor antagonist, PD 123319, on systemic and renal hemodynamics in conscious, chronically instrumented lambs aged approximately 1 and approximately 6 weeks of postnatal life. Mean arterial pressure (MAP), mean venous pressure (MVP), and renal blood flow (RBF) were measured for 10 min before and for 120 min after ZD 7155, PD 123319, or vehicle. In both age groups, administration of ZD 7155 decreased renal vascular resistance (RVR) and increased RBF within 5 min.

Modulation of systemic and renal haemodynamics by kappa-opioids in conscious lambs.

The purpose of the present study was to determine the cardiovascular effects of the kappa-opioid receptor agonist U-50488H at two stages of postnatal maturation under physiological conditions. Experiments were carried out firstly to define systemic and renal haemodynamic responses to kappa-opioid receptor activation and, secondly, to determine whether these effects are altered during postnatal maturation. To investigate whether the responses to U-50488H resulted from receptor-dependent effects, responses to U-50488H were also tested in the presence of the specific kappa-opioid receptor antagonist 5'-guanidinonaltrindole (GNTI).

Nitric oxide modulates renal vasoconstrictor effect of endothelin-1 in conscious lambs.

To test the hypothesis that nitric oxide (NO) buffers the renal vasoconstrictor effects of endothelin-1 (ET-1) early in life, renal haemodynamic responses to ET-1 were measured in the presence and absence of endogenously produced NO in conscious lambs. Renal haemodynamic effects of ET-1 were measured for 5 min before (control) and 20 min after intraarterial injection of ET-1 before and after pretreatment with 20 mg/kg of the L-arginine analogue N(G)-nitro-L-arginine methyl ester (L-NAME), (experiment 1) and its inactive isomer D-NAME (experiment 2) in conscious lambs aged approximately 1 week (N=7) and approximately 6 weeks (N=6). The two experiments were carried out in random order at intervals of 24-48 h.

Dose-dependent systemic and renal haemodynamic effects of angiotensin II in conscious lambs: role of angiotensin AT1 and AT2 receptors.

The present experiments were designed to measure the effects of acute administration of angiotensin (ANG) II on mean arterial pressure (MAP) and renal blood flow (RBF) in conscious, chronically instrumented lambs at two different stages of postnatal maturation, and to determine the receptors through which these effects of ANG II are elicited. Experiments consisted of haemodynamic measurements for 10 s before (Control) and for 60 s after intravenous (i.v.

Age-dependent cardiovascular, renal and endocrine responses to furosemide in conscious lambs.

1. The present study was performed to investigate some of the physiological responses to furosemide during postnatal maturation. 2.

Age-dependent effects of captopril on the arterial baroreflex control of heart rate in conscious lambs.

To test the hypothesis that angiotensin (ANG) II modulates the arterial baroreflex control of heart rate (HR) in an age-dependent manner, various parameters governing the arterial baroreflex control of HR were assessed before and after removal of endogenously produced ANG II by administration of the angiotensin-converting enzyme (ACE) inhibitor, captopril, to conscious, chronically instrumented lambs aged approximately 1 week (8 +/- 1 days; n = 8) or approximately 6 weeks (46 +/- 5 days; n = 8). After administration of captopril, systolic, diastolic and mean arterial pressures decreased significantly from control levels and HR increased; however, the effects were greater in 1- than in 6-week-old lambs. In 1-week-old lambs, after administration of captopril, there was also a significant increase in the slope coefficient, a decrease in minimum HR and a decrease in the point of maximum gain.

Renal responses to hemorrhage are age dependent in conscious sheep.

Experiments were carried out in conscious, chronically instrumented lambs (n = 8) and young adult sheep (n = 11) to investigate age-dependent renal responses to hemorrhage. Various parameters of renal function were measured for 1 h before and 1 h after either 10% hemorrhage (experiment 1) or 20% hemorrhage (experiment 2). The two experiments were carried out in random order at intervals of 2-5 days.

Techniques for recording renal sympathetic nerve activity in awake, freely moving animals.

The methods described here allow recording of sympathetic nerve discharge in awake, freely moving animals, and follow a historical perspective of the different techniques developed over the years to record sympathetic discharge. The length of time each system is viable for recording varies from days to weeks. Also included are special hints for the surgical implantation of recording electrodes, types of recording electrodes and cables, as well as the minimum equipment necessary for recording sympathetic discharge.

Renal sympathetic nerves do not modulate renal responses to haemorrhage in conscious lambs.

The present study was designed to investigate the renal responses to hypotensive haemorrhage early in life and the role of renal sympathetic nerves in modulating these renal responses. To this end, experiments were carried out in conscious, chronically instrumented lambs with either intact renal nerves (n = 7, Intact) or bilateral renal denervation performed at the time of surgery (n = 5, Denervated). Parameters of renal function were measured before and after 20% haemorrhage (experiment 1) and 0% haemorrhage (experiment 2), the latter serving as a time control.

Endothelin-1 produces no renal vasoconstriction in conscious newborn lambs.

Experiments were carried out to investigate the effects of endothelin-1 (ET-1) on renal vascular tone during development under physiological conditions in conscious lambs. Renal blood flow (RBF), renal vascular resistance (RVR), mean arterial pressure (MAP), and heart rate (HR) were measured in conscious, chronically instrumented lambs aged approximately 1 week and 6 weeks before and after intra-arterial (i.a.

Glomerular and tubular responses to N(G)-nitro-L-arginine methyl ester are age dependent in conscious lambs.

The present experiments were carried out to investigate the role of endogenously produced NO in modulating renal function during postnatal maturation under physiological conditions. In conscious, chronically instrumented lambs aged approximately 1 (n = 8) and approximately 6 wk (n = 8) of postnatal life, various parameters of glomerular and tubular function were measured for 1 h before and 1 h after intravenous injection of 20 mg/kg of N(G)-nitro-L-arginine methyl ester (L-NAME; experiment 1) or its inactive isomer D-NAME (experiment 2). After administration of L-NAME to 1-wk-old lambs, glomerular filtration rate (GFR) and filtration factor (FF) decreased by approximately 50% at 20 min, remaining decreased at 60 min.