Angiotensin II and VEGF are involved in angiogenesis induced by short-term exercise training.

Results from our laboratory have suggested a pathway involving angiotensin II type 1 (AT(1)) receptors and vascular endothelial growth factor (VEGF) in angiogenesis induced by electrical stimulation. The present study investigated if similar mechanisms underlie the angiogenesis induced by short-term exercise training. Seven days before training and throughout the training period, male Sprague-Dawley rats received either captopril or losartan in their drinking water. Rats underwent a 3-day treadmill training protocol. The tibialis anterior and gastrocnemius muscles were harvested under anesthesia and lightly fixed in formalin (vessel density) or frozen in liquid nitrogen (VEGF expression). In controls, treadmill training resulted in a significant increase in vessel density in all muscles studied. However, the angiogenesis induced by exercise was completely blocked by either losartan or captopril. Western blot analysis showed that VEGF expression was increased in the exercised control group, and both losartan and captopril blocked this increase. The role of VEGF was directly confirmed using a VEGF-neutralizing antibody. These results confirm the role of angiotensin II and VEGF in angiogenesis induced by exercise.

Effects of a normothermic dressing on pressure ulcer healing.

OBJECTIVE: To determine the effects of radiant heat applied through a semiocclusive dressing on periwound skin temperature and wound healing. DESIGN: Before-after trial. SETTING: Spinal cord injury and geriatric units of a VA medical center. PATIENTS: Twenty inpatients with 21 Stage III and IV pressure ulcers. INTERVENTIONS: A semiocclusive, heated dressing was applied to 15 Stage III and IV pressure ulcers for 4.5 hours, Monday through Friday, for 4 consecutive weeks. The dressing emitted heat at 38.0 degrees C for 2 60-minute periods daily. At all other times, the wounds received only standard wound care. Six wounds in a separate control group received only standard wound care during the same 4-week period. MAIN OUTCOME MEASURES: Periwound skin temperature within and adjacent to the dressing and measurements of wound surface area. MAIN RESULTS: Mean skin temperatures inside and outside the heated dressing increased by 0.97 degree C and 1.08 degrees C (P < .05), respectively, from baseline values. Wounds treated with standard care plus the heated dressing underwent a statistically significant reduction in mean surface area of 60.73%. Wounds in the control group underwent a statistically insignificant reduction in mean surface area of 19.24%. CONCLUSION: Wounds treated with a radiant heat dressing healed significantly faster than wounds that received only standard care. There were no adverse effects from the radiant heat dressing.

Influence of hip position and gender on active hip internal and external rotation.

A general lack of descriptive details exists for measurements of hip rotation range of motion. This study was designed to establish the influence of gender and hip flexion position on active range of motion of the hip in external and internal rotation. Sixty (39 females and 21 males) healthy college-age (21.8 +/- 1.7 years) subjects were studied. Hip rotation of the dominant leg of each subject was measured in the prone (hip near 0 degree of flexion) and seated (hip near 90 degrees of flexion) positions using a standard goniometer. Data were analyzed using an analysis of variance model. Pearson's r statistics were used to determine the degree of association between measurements of hip rotation made seated vs. prone. A statistically significant difference (p < 0.05) was found between mean hip external rotation (ER) measured seated (36 +/- 7 degrees) and mean hip ER measured prone (45 +/- 10 degrees). Conversely, mean hip internal rotation (IR) measured seated (33 +/- 7 degrees) was not statistically different than mean hip IR measured prone (36 +/- 9 degrees). Females had statistically more active hip internal and external rotation than males (p < 0.05). A moderate degree of association existed between measurements of hip ER taken in the prone vs. seated position (r = 0.57, p < 0.05). For IR, the degree of association between the two measurement positions was slightly higher (r = 0.72, p < 0.05). Unlike the amount of active hip internal rotation which showed little difference between measurements made prone vs. seated, our data indicate that measurement position had a significant effect on the amount of active range of motion of the hip in ER. These findings are clinically significant for they stress the importance of documenting measurement position. They also stress the need for representative norms to be established for each hip position and gender.

Gender-specific protection from microvessel rarefaction in female hypertensive rats.

Epidemiologic studies reveal that women have a significantly lower age-adjusted morbidity and mortality from cardiovascular disease than men, suggesting that gender is a cardiovascular disease risk factor. The mechanism of the "gender protection" is unknown. In this study, we investigated the microvascular remodeling in reduced renal mass plus a high salt (4.0% NaCl) diet model of hypertension (RRM + HS). We hypothesized that women would be protected from the increase in blood pressure and from the microvascular rarefaction associated with RRM + HS hypertension. Studies were designed to determine whether female rats were less susceptible to changes in microvessel density during RRM + HS. Microvessel density was measured in male and female low salt (0.4% LS) sham-operated controls (Sham + LS) and after 3 days or 4 weeks of RRM + HS hypertension. The microcirculation of hind limb (medial and lateral gastrocnemius, plantaris, soleus) muscles was visualized using rhodamine-labeled Griffonia simplicifolia I lectin. Tissue sections were examined by videomicroscopy and microvessel density was determined by quantitative stereology. As shown previously, mean arterial pressure increased to 160 +/- 8 mm Hg and microvessel density decreased (>30% decrease in all beds) in male RRM + HS. In contrast, mean arterial pressure of female RRM + HS rats was modestly increased from 101 +/- 2 to 118 +/- 4 mm Hg. Despite previous results showing a reduction in microvessel density of both normotensive and hypertensive male rats on a high salt diet, microvessel density of female RRM + HS rats was not reduced at either time. These results suggest that gender protection in the RRM rat extends beyond an attenuation of the increase in pressure to an immunity from microvascular rarefaction.

Effect of exposure to hypoxia from birth on aldosterone in rabbits: role of unesterified fatty acids.

Hypoxia and fluid and electrolyte disturbances are serious risks to normal postnatal development. Because a decrease in inspired O2 (hypoxic hypoxia) inhibits aldosterone synthesis in the adult and aldosterone controls water and electrolyte balance, we studied adrenocortical function in rabbits exposed to normobaric normoxia or hypoxic hypoxia (fraction of inspired O2 0.09) from birth. At 21 days of age, rabbits were anesthetized, the adrenals were rapidly removed, and the adrenal capsules containing mostly zona glomerulosa cells were separated. Cells were dispersed with collagenase and studied in vitro. Hypoxia in vivo resulted in a 73% decrease in basal aldosterone release and a 86% decrease in adenosine 3',5'-cyclic monophosphate-stimulated aldosterone release in vitro. We hypothesized that increased unesterified fatty acids could be partly responsible for inhibition of aldosterone synthesis. Total serum unesterified fatty acids in hypoxic kits were significantly increased (298 +/- 14 micromol/l) compared with normoxic kits (184 +/- 31 micromol/l). When cells from hypoxic rabbits were washed with fatty acid-free albumin and studied under conditions devoid of fatty acids, aldosterone production was partially restored. Corticosterone production was not affected by washing. Washing had no effect on aldosterone synthesis by cells from normoxic rats. Finally, exposing washed zona glomerulosa cells to oleic acid (10-50 microM) inhibited aldosteronogenesis. We conclude that exposure to hypoxia from birth attenuates aldosterone production in part due to an increase in levels of unesterified fatty acid levels.

Corticosterone inhibition of osmotically stimulated vasopressin from hypothalamic-neurohypophysial explants.

Glucocorticoids inhibit and glucocorticoid deficiency increases vasopressin (AVP) release in vivo. To determine whether the effect of glucocorticoids is hypothalamic and mediated via a glucocorticoid receptor, explants of the hypothalamic-neurohypophysial system were used to measure AVP release during agonist and antagonist exposure. Explants from adult rats, which contained AVP neurons of the supraoptic nucleus with axonal projections terminating in the neural lobe but excluded the paraventricular nucleus, were perifused with an osmotic stimulus (increase of 5 mosmol/h over 6 h) in the absence or presence of corticosterone (100 micrograms/dl) or with corticosterone (100 micrograms/dl) in the absence or presence of the glucocorticoid antagonist RU-486 (10 microM). AVP release was not increased during osmotic stimulation in the presence of corticosterone (Cort) and was 20-30% lower than osmotically stimulated release observed in the absence of Cort. RU-486 reversed the inhibitory effect of corticosterone on AVP release. No changes in AVP mRNA content were detected. These results suggest that Cort inhibits osmotically stimulated AVP release by a direct effect within the hypothalamus and/or neurohypophysis. This effect is mediated by the glucocorticoid receptor through either genomic or nongenomic mechanisms.

Vasopressin responses to corticotropin-releasing factor and hypertonicity after truncal vagotomy in dogs.

Infusion of corticotropin-releasing factor (CRF) augments the plasma vasopressin response to infusion of hypertonic saline in conscious dogs. Furthermore, afferent vagal nerve input from the abdomen is involved in the control of vasopressin release and may be altered by CRF. The purpose of the present study was to characterize the effect of CRF on the vasopressin response to hypertonic saline and to determine if it is mediated by afferent input carried from the abdominal vagus. Conscious male dogs (n = 5) underwent infusion of isotonic saline (vehicle), CRF (10 or 20 ng.kg-1.min-1), hypertonic saline (0.2 mmol.kg-1.min-1), or the combination of CRF and hypertonic saline. Hypertonic saline increased plasma sodium from 147 +/- 1 to 153 +/- 1 meq/1 and plasma vasopressin from 2.5 +/- 0.1 to 5.8 +/- 0.4 pg/ml. CRF infusion alone had no effect on plasma vasopressin. The addition of 10 or 20 ng.kg-1.min-1 CRF augmented the vasopressin response to hypertonic saline to 7.7 +/- 1.7 and 6.9 +/- 0.3 pg/ml, respectively. Truncal vagotomy did not attenuate the vasopressin response to hypertonic saline with or without CRF infusion. We conclude that CRF augments the vasopressin response to hypertonic saline and that this effect is not mediated via afferents from the abdominal vagus.

Aldosterone release from adrenal cells is inhibited by reduced oxygen levels in vitro during maturation in rabbits.

Hypoxia in vivo leads to a decrease in aldosterone not completely explained by extrinsic controllers of adrenal function including adrenocorticotrophic hormone, renin-angiotensin II, and K+. The dissociation of renin and aldosterone during acute hypoxia in vivo may be explained by the finding that aldosterone synthesis in adrenal cells is reversibly and specifically inhibited by decreases in O2 levels within the physiological range. The present study investigated whether the direct effect of acute decreases in O2 levels on aldosteronogenic pathway is altered during maturation. Adrenal cells (whole adrenals) were prepared from fetal (27 days gestation), neonatal (1 day), and infant (10 days) New Zealand White rabbits, and capsular cells were prepared from young (21 days) and adult (3 months) rabbits. All cells were dispersed with collagenase. Basal and cAMP-stimulated aldosterone production were assessed under two different levels of O2 (pO2 = 20.0 kPa or pO2 = 8.7 kPa). Decreased O2 levels significantly inhibited cAMP-stimulated aldosterone production in cells obtained from rabbits of all ages by 60 +/- 5% cAMP-stimulated aldosterone production was significantly lower in cells obtained from neonates and premature animals under both normoxic and reduced O2 conditions as compared with animals > or = 10 days old. Corticosterone production by cells obtained from adults and 21-day-old rabbits was unaffected by reduced O2 conditions suggesting a specific effect on the aldosterone pathway. The data demonstrate that the O2 sensitivity of the aldosterone pathway is present throughout development.

Hypertension induced by high salt intake in absence of volume retention in reduced renal mass rats.

Reduction of renal mass (RRM) combined with a high-salt diet results in volume retention, a rise of cardiac output, and hypertension. The present studies were designed to determine whether prevention of volume retention would alter the rise of mean arterial pressure (MAP) in RRM rats given high salt. Rats were studied in a modified metabolic cage to permit continuous determination of total body weight (TBW). In group 1, NaCl was increased from 1 to 14.5 meq/day and delivered isotonically. In group 2, NaCl was increased while TBW was servo-controlled to a constant level. Group 3 was also servo-controlled, but rats received an intravenous infusion of an arginine vasopressin V1 antagonist throughout the study. MAP in group 1 rose 24 mmHg by day 4 of high salt with a parallel increase of TBW of 26 g. In group 2, MAP rose 48 mmHg by day 4 of high salt, while TBW was controlled to within 0.6% of control body weight. With inhibition of vasopressin V1 receptors (group 3), MAP rose 39 mmHg. Nearly equivalent amounts of NaCl were retained in all groups, which was associated with no change of plasma Na in group 1 but an increase of nearly 7 meq/ml in groups 2 and 3. Hematocrit fell nearly 9% in groups 2 and 3 compared with a 4% reduction in group 1. The results suggest that under conditions where net retention cannot occur, high salt intake increases MAP by an osmotically driven fluid transfer from cells, which results in an even greater expansion of blood volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic physiological increases in cortisol inhibit the vasopressin response to hypertonicity in conscious dogs.

Chronic increases in cortisol inhibit basal plasma arginine vasopressin (AVP). Acute pretreatment with cortisol inhibits the large increase in AVP during hypotension or hypoxia but does not inhibit the modest increase in AVP in response to hypertonic saline (HS). We evaluated the effect of a chronic increase in cortisol (physiological range) on the acute AVP response to HS. Five male dogs received a continuous infusion of either vehicle or cortisol (65 mg/day) for 7 days. The AVP response to HS (0.2 mmol.kg-1.min-1 for 30 min) was tested before infusion, on days 1, 4, and 7 of chronic infusion, and 2 days after the infusion was discontinued. Plasma cortisol increased significantly from 1.0 +/- 0.2 micrograms/dl to an average over the 7 days of infusion of 5.0 +/- 0.2 micrograms/dl, and basal plasma AVP was significantly decreased during cortisol infusion. The increase in plasma Na and osmolality during HS was unaffected by chronic infusion. HS resulted in an increase in AVP from 3.5 +/- 0.2 to 7.1 +/- 0.7 pg/ml before cortisol infusion. After 7 days of cortisol, the AVP response to HS (from 2.6 +/- 0.1 to 3.9 +/- 0.7 pg/ml) was significantly attenuated. Sustained, physiological increases in cortisol significantly inhibited osmotically stimulated AVP release. The decrease in AVP during hypercortisolism and the syndrome of inappropriate antidiuretic hormone in patients with adrenal insufficiency appear to be due to an inhibitory effect of cortisol on the osmotic sensitivity of the AVP control system.

The effect of intracarotid vasopressin infusion on ACTH release in neurohypophysectomized, conscious dogs.

Neurohypophysectomy (NHX) attenuates the adrenocorticotropic hormone (ACTH) response to arterial hypotension but not corticotropin-releasing hormone (CRH) or insulin-induced hypoglycemia in conscious dogs. The purpose of the present study was to determine if increasing vasopressin (AVP) in the cephalic circulation by carotid infusion normalizes the ACTH response to hypotension attenuated by NHX. Five male, conditioned dogs underwent controlled, acute decreases in arterial pressure (by approximately 25 mmHg) by infusion of sodium nitroprusside (NP) before and > 4 wk after selective NHX. ACTH increased from 40 +/- 3 to 242 +/- 79 pg/ml during NP in the intact state. This response was greatly attenuated after NHX (peak ACTH 81 +/- 15 pg/ml). Simultaneous intravenous infusion of AVP (12.5 ng/min) had a small, augmenting effect on the ACTH response to NP (peak ACTH 120 +/- 27 pg/ml). Intracarotid AVP (12.5 ng/min) greatly augmented the ACTH response to NP (peak ACTH 202 +/- 26 pg/ml) such that it was no longer different from the intact response. Neither intravenous nor intracarotid AVP infusion per se had a great effect on ACTH. A normal ACTH response to hypotension requires an intact neurohypophysis and is mediated by a cephalic action of magnocellular AVP.

Physiological increases in cortisol inhibit basal vasopressin release in conscious dogs.

Glucocorticoid deficiency leads to elevated plasma vasopressin (AVP), while chronic endogenous hypercortisolism may inhibit osmotically stimulated AVP, suggesting that glucocorticoids may be feedback inhibitors of AVP secretion. We evaluated the effect of physiological increases in cortisol (65 mg/day iv) for 7 days on basal AVP and oxytocin (OT) in five conscious, male dogs. Cortisol increased from 1.3 +/- 0.1 to 5.0 +/- 0.8 micrograms/dl during infusion. Basal plasma AVP significantly decreased from 3.5 +/- 0.2 to 2.6 +/- 0.3 pg/ml during cortisol infusion. Plasma OT, osmolality, and sodium did not change while arterial pressure decreased (from 107 +/- 3 to 102 +/- 2 mmHg) on days 4 and 6. Increases in cortisol led to a physiologically significant, nonosmotic decrease in AVP. The effect was specific to AVP and independent of changes in arterial pressure. Glucocorticoid administration significantly decreased basal AVP within 24 h, which is comparable to the negative feedback control of adrenocorticotropic hormone. The inverse relationship between cortisol and AVP may account for the nonosmotic change in AVP in patients with disorders of glucocorticoid secretion.

Effect of chronic renal medullary nitric oxide inhibition on blood pressure.

The effects of chronic nitric oxide inhibition in the renal medulla on renal cortical and medullary blood flow, sodium balance, and blood pressure were evaluated in conscious uninephrectomized Sprague-Dawley rats. During a 5-day renal medullary interstitial infusion of the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 120 micrograms/h) in saline (0.5 ml/min), renal medullary blood flow was selectively decreased by 30% after 2 h and was maintained at that level for the entire infusion. The decrease in medullary blood flow was associated with sodium retention and increased blood pressure. After the cessation of L-NAME infusion, medullary blood flow returned to control, and the sodium balance became negative as blood pressure returned to baseline. These data indicate that renal medullary nitric oxide plays an important role in the regulation of renal blood flow, sodium excretion, and blood pressure.

Chronic pressure-natriuresis relationship in dogs with inherited essential hypertension.

A genetic model of essential hypertension in the dog was studied to describe the phenotypic expression of the arterial pressure, as well as to determine the relationship between mean arterial blood pressure (MAP), hormone, and renal excretory responses to four different levels of sodium intake (5, 40, 120, 240 mEq/day) delivered intravenously and isotonically. This model was developed at the University of Pennsylvania (U/Penn) and termed Pennsylvania hypertensive dogs (PHD). The MAP was recorded beat-by-beat, 24 h/day, in 16 dogs. Water and sodium balances were determined daily for 4 days at each level of intake and blood samples were collected on the last day of each salt step for analysis of plasma renin activity (PRA), atrial natriuretic peptide (ANP), aldosterone (ALDO), and vasopressin (AVP). After the study, the dogs were designated as hypertensive (PHD-HT) when the 24-h average MAP was greater than 110 mm Hg and systolic pressure was greater than 160 mm Hg. Dogs that failed to meet both criteria were designated as normotensive genetic controls (PHD-NT). Although sodium was retained during the first day of each increase of salt intake in both groups, a return to balance was observed within the 4 days. There was no apparent change in the slope of the chronic renal function curve in either group of PHD studied, although the PHD-HT exhibit a curve shifted to a higher level of MAP. Plasma hormone levels in both groups of PHD studied responded in a manner similar to normal mongrel dogs with reductions of PRA, ALDO, elevations of ANP, and no change in AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of a reduction in sodium intake on cold-induced elevation of blood pressure in the rat.

Chronic exposure of rats to cold (5 degrees C) induces hypertension within 3 weeks. The objective of this study was to determine the effect of treatment with graded levels of dietary NaCl on the induction of hypertension during chronic exposure to cold. Four groups of male rats were used. The first, given a commercial sodium-deficient diet containing 0.30% NaCl, served as the warm-adapted control group. The second, third, and fourth groups were given the same diet containing 0.075%, 0.15%, and 0.30% NaCl, respectively. Because cold-exposed rats ingest approximately twice as much food as warm-adapted controls, this represented half, the same, and twice the amount of NaCl ingested by the control group. The latter three groups were placed in cold air (5 degrees C). All cold-treated groups had an elevation of systolic blood pressure that was proportional to the concentration of NaCl in the diet by the seventeenth week of exposure to cold. Cardiac hypertrophy occurred to the same extent in all cold-exposed groups and was thus unaffected by the NaCl content of the diet or by the extent of elevation of blood pressure. Hence, cardiac hypertrophy during chronic exposure to cold is supported by other factors, possibly by the increased concentration of either norepinephrine or triiodothyronine, or both, which occurs characteristically in rats under these conditions. The results of this experiment suggest that the amount of NaCl ingested daily plays a role in the cold-induced elevation of blood pressure observed in rats.

Effect of hypotension and hyperosmolality on vasopressin and ACTH responses to hypoglycemia in conscious dogs.

The purpose of these studies was, first, to determine whether hypertonic saline (HS) infusion or nitroprusside (NiPr)-induced hypotension augments the vasopressin (AVP) and adrenocorticotropic hormone (ACTH) responses to insulin (Ins)-induced hypoglycemia and, second, to determine whether neurohypophysectomy could attenuate the augmentation. Conscious, male dogs (n = 8) underwent two different types of experiments. In the first, Ins was preceded by either a 30-min infusion of normal saline (control) or HS to raise plasma osmolality and AVP. HS augmented the AVP response but diminished the ACTH response to Ins. In the second group of experiments, Ins was preceded by a controlled decrease in mean arterial pressure using NiPr, which led to an increase in AVP and ACTH. The initial ACTH and AVP response to Ins was augmented by NiPr, but this early augmentation was not sustained. Neurohypophysectomy attenuated the early augmentation of the ACTH response to Ins by NiPr, but did not alter the final ACTH level achieved. We conclude that HS augmented the AVP but inhibited the ACTH response to Ins probably because of expansion of plasma volume. Concomitant hypotension led to an augmentation of the early but not sustained AVP and ACTH response to Ins. Neurohypophysectomy eliminated this augmentation, suggesting a role for AVP from the neural lobe in the early ACTH response to combined hypotension and Ins-induced hypoglycemia.

Role of the sympathetic nervous system in cold-induced hypertension in rats.

Hypertension develops in rats exposed chronically to cold [6 +/- 2 degrees C (SE)] and includes both an elevation of mean arterial pressure and cardiac hypertrophy. Previous studies suggest that cold-exposed animals, at least initially, have a large sustained increase in the activity of their sympathetic nervous system, suggesting a failure of the baroreceptor system to provide sufficient negative feedback to the central nervous system. The present study was designed to investigate whether alterations in the activity of the sympathetic nervous system, including the baroreceptor reflex, occur during exposure to cold and whether they contribute to cold-induced hypertension. Twenty male rats were prepared with indwelling catheters in the femoral artery and vein. Ten of the rats were exposed to cold (6 +/- 2 degrees C) chronically, while the remaining 10 were kept at 26 +/- 2 degrees C. Withdrawal of arterial blood samples (less than 5 ml/kg), measurement of direct arterial pressures, and measurement of baroreflex function were carried out at 0800 h at intervals throughout the experiment. Norepinephrine and epinephrine concentrations in plasma were also determined at intervals throughout the experiment. Systolic, diastolic, and mean blood pressures of cold-exposed rats were increased to levels significantly above those of controls. The sensitivity of the baroreflex (delta heart period/delta mean arterial pressure) was decreased in the cold-treated group. The concentration of norepinephrine in plasma increased after 24 h of exposure to cold and remained elevated throughout the experiment, whereas the concentration of epinephrine in plasma increased initially but returned to control levels after 19 days of exposure to cold.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of cold-induced increase in blood pressure of rats by captopril.

To assess the possibility that the renin-angiotensin system may play a role in the development of cold-induced hypertension, three groups of rats were used. Two groups were exposed to cold (5 +/- 2 degrees C) while the remaining group was kept at 26 +/- 2 degrees C. One group of cold-treated rats received food into which captopril (0.06% by weight) had been thoroughly mixed. The remaining two groups received the same food but without captopril. Systolic blood pressure of the untreated, cold-exposed group increased significantly above that of the warm-adapted, control group within 4 weeks of exposure to cold. In contrast, chronic treatment with captopril prevented the elevation of blood pressure. Rats were killed after 4 months of exposure to cold. At death, the heart, kidneys, adrenal glands, and interscapular brown fat pad were removed and weighed. Although captopril prevented the elevation of blood pressure in cold-treated rats, it did not prevent hypertrophy of the kidneys, heart, and interstitial brown adipose tissue that characteristically accompanies exposure to cold. Thus, chronic treatment with captopril prevented the elevation of blood pressure when administered at the time exposure to cold was initiated. It also reduced the elevated blood pressure of cold-treated rats when administered after blood pressure became elevated. This suggests that the renin-angiotensin system may play a role in the elevation of blood pressure during exposure to cold.

Changes in blood pressure and dipsogenic responsiveness to angiotensin II during chronic exposure of rats to cold.

Hypertension accompanies chronic exposure of rats to cold (5-6 degrees C). Systolic, diastolic, and mean blood pressures become elevated, and hypertrophy of the heart occurs. A previous study from this laboratory suggested that the renin-angiotensin system may play a role. The present study was carried out to assess this further. Thus, in addition to measurement of systolic blood pressure at intervals during exposure to cold, plasma renin activity and the dipsogenic responsiveness to acute administration of angiotensin II were also measured to assess the functional status of the renin-angiotensin system. The results showed a significant (p less than 0.05) increase in systolic blood pressure during the third week of exposure to cold. In contrast, plasma renin activity (PRA) increased within the first week of exposure to cold, and declined thereafter to reach the level of the control by the third week of exposure to cold. By the fourth week, PRA decreased to a level significantly (p less than 0.05) below that of the control group. The responsiveness to acute administration of angiotensin II (AII), as assessed by the drinking response, increased significantly (p less than 0.05) by the third week of exposure to cold and remained significantly elevated during the fourth week. There was a significant (p less than 0.01) direct relationship between dipsogenic responsiveness to AII and blood pressure in the cold-treated (r = .57), but not the control group (r = .12). There was also a significant (r = -.91) indirect linear relationship between PRA and dipsogenic responsiveness to AII. Cold-treated rats had significant increases in urinary norepinephrine output and weights of heart, kidneys, adrenals, and brown adipose tissue characteristic of rats acclimated to cold.(ABSTRACT TRUNCATED AT 250 WORDS)

ACTH and vasopressin responses to insulin-induced hypoglycemia in intact and neurohypophysectomized conscious dogs.

Factors from the neurohypophysis are important in the control of anterior pituitary function. This study evaluated the hypothesis that the neurophypophysis is an integral component of the adrenocorticotropin (ACTH) response to certain stimuli. Furthermore, we investigated the possibility that the importance of the neurohypophysis during corticotropic stimuli can be classified by the magnitude of the systemic vasopressin response induced. The ACTH response to insulin-induced hypoglycemia (INS), nitroprusside hypotension (NP), or ovine corticotropin-releasing factor (CRF) infusion (20 ng/kg/min) was measured in dogs before (intact) and greater than 2 weeks after selective transbuccal neurohypophysectomy (NHX). INS (0.2 U/kg) resulted in a significant decrease in plasma glucose from 93 +/- 1 to 33 +/- 2 mg/dl at 30 min and a significant increase in plasma ACTH from 53 +/- 10 to 306 +/- 33 pg/ml in intact dogs whereas the vasopressin (AVP) response was small (2.8 +/- 0.3 to 5.5 +/- 0.7 pg/ml). NHX had no effect on the blood glucose or ACTH response to INS. NP resulted in large increases in ACTH from 54 +/- 8 to 351 +/- 89 pg/ml and in AVP from 2.7 +/- 0.2 to 272 +/- 98 pg/ml. In contrast to INS, NHX significantly attenuated the ACTH and AVP responses to NP. The ACTH response to CRF was not attenuated by NHX, indicating normal pituitary corticotropic function. In summary, NHX attenuated the ACTH response to hypotension (large peripheral AVP response) but not to INS or CRF (small peripheral AVP response).(ABSTRACT TRUNCATED AT 250 WORDS)