Renin and heart rate responses to haemorrhage are age dependent in conscious lambs.

The present experiments were carried out in conscious lambs (1-2 weeks old, n = 9) and older sheep (11-12 weeks old, n = 11) to determine whether the cardiovascular and endocrine responses to 0, 10 and 20 % haemorrhage were developmentally regulated. The major novel finding of our study is that throughout the first 3 months of postnatal life, there is a similar decrease in mean arterial pressure and a similar restoration of pressure to pre-haemorrhage levels, for the same degree of blood loss, yet the mechanisms used to restore pressure appear to be age dependent as follows. In lambs, but not in older sheep, heart rate increased for 1 h after 20% haemorrhage. Activation of the renin-angiotensin system was also greater and more prolonged in lambs than in older sheep following haemorrhage, and occurred at a lesser degree of blood loss. Plasma arginine vasopressin responses to haemorrhage were, however, similar in both age groups. These data provide new information that some of the mechanisms used to restore arterial pressure following blood volume depletion appear to be age dependent.

Baroreceptors, alpha1-adrenergic receptors, and regulation of mesenteric blood flow.

In the mesenteric circulation of the rat a myogenic autoregulatory system operates at 0.1-0.15 Hz. Negative admittance phase in the region above 0.2 Hz suggested operation of an arterial baroreflex. The present study was designed to test this interpretation and to identify the neurotransmitter involved. In rats anesthetized with isoflurane, blood pressure and mesenteric blood flow (transit time ultrasound) were measured with central mechanisms intact, after sinoaortic denervation, and after denervation of the mesenteric bed. Sinoaortic denervation abrogated the negative phase in the band from 0.3 to 0.6 Hz and increased admittance gain in this region. Subsequent mesenteric denervation had no further effect on the pressure-flow transfer function. In a separate experiment, alpha1-adrenergic blockade reduced, but did not remove, the negative admittance phase in the 0.2- to 0.5-Hz band without altering admittance gain. It is concluded that the baroreflex acting on the mesenteric circulation can be identified by admittance phase, but that admittance gain is uninformative. Part of the response is mediated by alpha1-adrenergic transmission.

Vascular, renal, and endocrine responses to low-dose atrial natriuretic peptide in the fluid-balanced New Zealand genetically hypertensive rats with and without endogenous arginine vasopressin.

In hypertension, the relationship between atrial natriuretic peptide (ANP) and vasopressin (AVP) is not yet clear, although their renal actions are effectively autoregulation. To examine the possible interaction further, the responses to ANP infusion (75 ng x min (-1), i.v.) have been investigated in both hypertensive and normotensive AVP-replete (HT and NT) and AVP-deficient (HTDI and NTDI) rats. This study aimed to assess the renal function and the plasma hormone concentrations of AVP, angiotensin II (AII), ANP, aldosterone, and corticosterone in the conscious, chronically catheterized, fluid-balanced rats, and to examine the cardiovascular, renal, and endocrine responses to a constant infusion of a low-dose ANP. Data gained from the present study showed, for the first time, the hormone profile, plasma electrolyte composition, and detailed renal function of the servo-controlled, fluid-balanced rats. The similarities of plasma electrolyte composition between servo-controlled and untreated rats indicated that the servo-controlled fluid replacement technique maintained the differences between the strains and maintained body fluid balance during the experimental periods. Following ANP administration, there were no changes in glomerular filtration rate (GFR) in all groups, but an enduring diuresis and natriuresis were observed in HT and NT, which were milder in HTDI rats. However, the hypotensive effect of ANP was of a similar magnitude in all rat strains. HTDI rats exhibited an inhibition of the renin-angiotensin system (RAS), which may have participated in the reduced mean arterial blood pressure (MAP) and natriuresis observed in these rats. The renal actions of ANP appear to rely upon renal tubular events, as indicated by increased fractional electrolyte excretions in the AVP-replete rats. This study highlights the importance of AVP to the profile of the renal actions of ANP in normal rats.

Responses of mesenteric and renal blood flow dynamics to acute denervation in anesthetized rats.

Previous studies have shown that renal autoregulation dynamically stabilizes renal blood flow (RBF). The role of renal nerves, particularly of a baroreflex component, in dynamic regulation of RBF remains unclear. The relative roles of autoregulation and mesenteric nerves in dynamic regulation of blood flow in the superior mesenteric artery (MBF) are similarly unclear. In this study, transfer function analysis was used to identify autoregulatory and baroreflex components in the dynamic regulation of RBF and MBF in Wistar rats and young spontaneously hypertensive rats (SHR) anesthetized with isoflurane or halothane. Wistar rats showed effective dynamic autoregulation of both MBF and RBF, as did SHR. Autoregulation was faster in the kidney (0.22 +/- 0.01 Hz) than in the gut (0.13 +/- 0.01 Hz). In the mesenteric, but not the renal bed, the admittance phase was significantly negative between 0.25 and 0. 7 Hz, and the negative phase was abrogated by mesenteric denervation, indicating the presence of an arterial baroreflex. The baroreflex was faster than autoregulation in either bed. The presence of sympathetic effects unrelated to blood pressure was inferred in both vascular beds and appeared to be stronger in the SHR than in the Wistar rats. It is concluded that a physiologically significant baroreflex operates on the mesenteric, but not the renal circulation and that blood flow in both beds is effectively stabilized by autoregulation.

Renal denervation alters cardiovascular and endocrine responses to hemorrhage in conscious newborn lambs.

To investigate the role of renal sympathetic nerves in modulating cardiovascular and endocrine responses to hemorrhage early in life, we carried out three experiments in conscious, chronically instrumented lambs with intact renal nerves (intact; n = 8) and with bilateral renal denervation (denervated; n = 5). Measurements were made 1 h before and 1 h after 0, 10, and 20% hemorrhage. Blood pressure decreased transiently after 20% hemorrhage in intact lambs and returned to control levels. In denervated lambs, however, blood pressure remained decreased after 60 min. After 20% hemorrhage, heart rate increased from 170 +/- 16 to 207 +/- 18 beats/min in intact lambs but not in denervated lambs, in which basal heart rates were already elevated to 202 +/- 21 beats/min. Despite an elevated plasma renin activity (PRA) measured in denervated (12.0 +/- 6.4 ng ANG I . ml-1 . h-1) compared with intact lambs (4.0 +/- 1.1 ng ANG I . ml-1 . h-1), the increase in PRA in response to 20% hemorrhage was similar in both groups. Plasma levels of arginine vasopressin increased from 11 +/- 8 to 197 +/- 246 pg/ml after 20% hemorrhage in intact lambs but remained unaltered in denervated lambs from baseline levels of 15 +/- 10 pg/ml. These observations provide evidence that in the newborn, renal sympathetic nerves modulate cardiovascular and endocrine responses to hemorrhage.

Endocrine effects of pregnancy and exposure to a simulated open field in rats.

In adult rats, exposure to a novel environment, such as a simulated open field, elicits an increase in body core temperature. We have recently shown that this response is attenuated in midpregnancy and abolished at term of pregnancy in rats. We postulated that this gestation-dependent response resulted from alterations in the hypothalamic-pituitary-adrenal axis. To test this hypothesis, we measured the effects of pregnancy on renin, corticosterone, and arginine vasopressin (AVP) responses to exposure to either a simulated open field (30 or 120 min) or to the home cage (30 or 120 min) in rats. Pregnancy increased renin and corticosterone levels but not plasma AVP levels. Exposure to an open field decreased renin and increased plasma AVP levels in nonpregnant rats and on days 15 and 20 of gestation in pregnant rats, compared with home cage responses. Serum corticosterone levels were elevated after exposure to an open field in nonpregnant and pregnant rats, compared with home cage rats, the effect being more prolonged on day 20 of gestation. These observations provide new information on endocrine changes during pregnancy in rats and may help to explain the attenuated stress-induced hyperthermic response to exposure to a novel environment seen near term of pregnancy.

Systemic and renal hemodynamic effects of hemorrhage in conscious lambs.

The purpose of the present study was to investigate the systemic and renal hemodynamic effects of hemorrhage in the newborn to determine whether the newborn is capable of restoring blood pressure in the face of blood loss at hemorrhage of up to 20% of vascular volume. Experiments were carried out in conscious, chronically instrumented lambs and consisted of measurements before, during, and after hemorrhage at 0 (n = 9), 10 (n = 8), 15 (n = 8), and 20% (n = 8) of blood volume. Right atrial pressure decreased but only after 20% hemorrhage. There was a transient decrease in blood pressure at 10-15% hemorrhage and a sustained decrease in blood pressure after 20% hemorrhage (from 82 +/- 7 to 66 +/- 9 mmHg). Heart rate increased transiently after 15% hemorrhage (from 173 +/- 32 to 204 +/- 66 beats/min); heart rate remained increased for 60 min after 20% hemorrhage from 171 +/- 17 to 214 +/- 31 beats/min. There were no changes in renal vascular resistance in response to hemorrhage of up to 20% of vascular volume. These observations provide evidence that the newborn is capable of buffering blood pressure in response to blood loss of up to 20% of vascular volume and that the renal bed does not appear to contribute to the restoration of blood pressure after blood loss early in life.