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B A Scoggins
Publications and source records attributed to B A Scoggins.
Pyrogenic stimulation of vascular resistance in conscious sheep.
Increased arterial blood pressure following a pyrogenic reaction has been reported in previous studies, however the mechanism of this hypertension has not been examined in detail. The present study investigated the effects of both intravenous (IV) and intracerebroventricular (ICV) injection of lipopolysaccharide (LPS) from E. coli on body temperature (Tb), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), calculated total peripheral resistance (CTPR), stroke volume (SV) and plasma levels of adrenocorticotropin (ACTH) and arginine vasopressin (AVP) in conscious, chronically instrumented sheep. IV injection of LPS (1 microgram) increased Tb in a biphasic manner from 38.7 +/- 0.1 to 39.5 +/- 0.2 degrees C after 50 min and to 39.9 +/- 0.2 degrees C after 130 min, and MAP increased biphasically from 64 +/- 1 to 70 +/- 4 mmHg after 40 min and to 78 +/- 3 mmHg after 130 min. CO initially decreased from 4.4 +/- 0.1 to 3.5 +/- 0.1 after 40 min followed by a secondary rise to 4.8 +/- 0.1 l/min after 100 min. This occurred together with a large, biphasic increase in CTPR from 14.5 +/- 1.0 to 22.0 +/- 2.0 mmHg/l/min at 40 min, and to 18.1 +/- 0.1 mmHg/l/min at 120 min. HR increased from 68 +/- 4 to 97 +/- 4 b/min and SV decreased from 65 +/- 2 to 41 +/- 4 ml/beat during the first phase of activation. Plasma ACTH increased from 22 +/- 9 to 1043 +/- 175 pg/ml after 80 min, and plasma AVP increased from 0.7 +/- 0.2 to 12 +/- 4.0 pg/ml after 60 min. ICV injection of LPS produced a long-lasting increase in Tb and MAP, but had no effect on HR or plasma AVP. Plasma ACTH increased from 30 +/- 12 to 427 +/- 110 pg/ml. These changes suggest that intravenous pyrogenic infection produces a potent vasoconstrictor action in sheep to increase blood pressure, possibly mediated by the actions of AVP within the CNS, or other pyrogenically released vasoconstrictor factors. Furthermore, the duration of activation of the cardiovascular system following peripheral and central LPS administration is different, which together with the contrasting effects on ACTH and AVP, indicate the involvement of several hypertensive mechanisms.
Adrenocorticotropic Hormone↗
Cardiovascular actions of atrial natriuretic factor in sheep with cardiac failure.
The present study examines in detail the short-term cardiovascular actions of atrial natriuretic factor (ANF) in sheep with experimental low-output cardiac failure. Five conscious sheep, surgically implanted with a ventricular pacing wire, were paced at 220 beats/min for 14 days. Most clinical symptoms of congestive heart failure (CHF) were apparent after the 14 days, characterized by low cardiac output, high venous pressure, increased total peripheral resistance, increased plasma levels of ANF, noradrenaline, arginine vasopressin and renin, and marked fluid retention. On day 14 of pacing, intravenous infusion of ANF at 100 micrograms/h for 60 min restored cardiac output to prepacing values and reduced both total peripheral resistance and right atrial pressure. These effects were sustained throughout the infusion period. No change was seen in blood pressure, plasma renin, or noradrenaline levels. These hemodynamic changes, produced by short-term infusion of ANF, contrasted with those seen in normal sheep, where there was a fall in cardiac output with increased total peripheral resistance. These changes reflect a return toward normal of the left ventricular function curve. This is the first study to report that ANF improves cardiac function in conscious sheep with CHF, primarily by a vasodilator action to reduce cardiac preload, and suggests that ANF may be useful in treating the hemodynamic effects associated with cardiac failure.
Animals↗
The effect of hypovolemia on the renal and cardiovascular responses to atrial natriuretic factor (ANF) infusion.
The renal and cardiovascular effects of ANF infusion have been examined in separate series of experiments; in conscious instrumented sheep following either hemorrhage (10 mL/kg body weight) or removal of 500 mL of plasma by ultrafiltration. Renal arterial infusion of hANF (99-126) at 50 micrograms/h increased sodium excretion from 99 +/- 30 to 334 +/- 102 (p less than 0.05) in normal animals, and from 77 +/- 31 to 354 +/- 118 mumol/min in hemorrhaged animals. Similarly in sheep following ultrafiltration, cardiac output and stroke volume were reduced by intravenous infusion of ANF (100 micrograms/h), although these effects were less marked than those observed in normal animals. The rapid modulation of natriuretic responses to ANF observed in volume expanded animals is not seen in this model of acute volume depletion suggesting that the mechanism through which the renal response to ANF is modulated in low sodium or volume states is not simply the reverse of that which produces rapid enhancement of response following blood volume expansion.
Animals↗
Haemodynamic and metabolic effects of short term administration of synthetic sex steroids in humans.
Synthetic sex steroid administration is a major cause of iatrogenic hypertension but little is known of the haemodynamic or metabolic consequences of these steroids. This study examined the short term blood pressure, volume and metabolic consequences of 5 day administration of synthetic androgen to normal men and synthetic oestrogen or progestogen to normal women. Healthy subjects (8 women, 6 men) on a constant diet took part in each of 3 studies. Males received testosterone undecanoate 120 mg/day (n = 6) and females either ethinyloestradiol 0.3 mg/day (n = 5) or norethisterone 15 mg/day (n = 6) for 5 days in the last week of the cycle. Norethisterone increased lying (+7 mmHg) and standing (+8 mmHg) systolic pressure but the other steroids did not alter blood pressure. All 3 treatments increased body weight. There were no consistent changes in plasma electrolytes or glucose with any steroid, and no urinary sodium retention or changes in urine Na:K ratio. Haematocrit fell on ethinyloestradiol but no steroid significantly increased plasma volume (measured as volume of distribution of 125I human serum albumin). Renin substrate and cortisol rose and renin concentration fell on ethinyloestradiol. These studies suggest that the progestogen component may contribute to the blood pressure raising effects of oral contraceptives.
Adult↗
Effects of calcium channel blockade on the hemodynamic responses to endothelin infusion in conscious sheep.
The hemodynamic responses to bolus injection of endothelin I (ET) at 5, 15, and 50 micrograms were examined in conscious sheep (n = 5) before and after infusion of nisoldipine at 25 micrograms/kg/h. Endothelin produced dose-dependent increases in mean arterial pressure (MAP + 87 +/- 6 mm Hg at 50 micrograms) and calculated total peripheral resistance (CTPR + 54 +/- 15 mm Hg/L/min at 50 micrograms) and decreases in heart rate (HR - 34 +/- 6 beats/min at 50 micrograms) and cardiac output (CO - 2.6 +/- 0.3 L/min at 50 micrograms) but no change in stroke volume (SV). Nisoldipine attenuated (P less than .05) the endothelin-induced changes in MAP (+26 +/- 3 mm Hg at 5 micrograms) and CTPR (+13.0 +/- 2.1 mm Hg/L/min at 50 micrograms), but not the fall in heart rate or cardiac output. These data are compatible with the hypothesis that vasoconstrictor effects of ET in sheep are in part dependent on influx of calcium through L-type channels.
Animals↗
The effect of uninephrectomy on osteocalcin metabolism in sheep: a direct evaluation of renal osteocalcin clearance.
Indirect evidence has suggested that the kidney is a major organ of clearance for osteocalcin, a circulating marker of osteoblast function. The objectives of the present study were (1) to confirm the role of the kidney in osteocalcin clearance (2) to quantify the contribution of extrarenal sites and (3) to investigate the renal mechanism(s) of osteocalcin clearance. Plasma osteocalcin levels, osteocalcin plasma clearance rate (PCR) and plasma production rate (PPR) were determined in oophorectomized (OX) and uninephrectomized oophorectomized (UOX) sheep. The osteocalcin renal extraction efficiency (REE) and the effective renal plasma flow (ERPF) were measured, and the osteocalcin renal clearance rate (RCR) was calculated. The osteocalcin PCR was reduced significantly in UOX compared with OX sheep (2.0 +/- 0.1 (n = 9) vs 2.5 +/- 0.1 litres/h (n = 44); P less than 0.0005). In UOX sheep with plasma creatinine levels less than or equal to 130 mumol/l, the osteocalcin REE was 9 +/- 1.3% and the osteocalcin RCR was 50-91% of osteocalcin PCR (n = 4). In UOX sheep with plasma creatinine levels in the range 100-440 mumol/l, there was a linear relationship between osteocalcin PCR and ERPF; the osteocalcin RCR was related to the osteocalcin PCR (RCR = 0.9 x PCR - 0.50). Intravenous infusion of the synthetic glucocorticoid triamcinolone acetonide (TA) in UOX sheep led to marked decrements in plasma osteocalcin levels and the osteocalcin PPR, and a significant increase in the osteocalcin PCR. These changes were accompanied by a 44% increase in ERPF.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Amiloride blocks the onset of ACTH-induced hypertension in the sheep.
This study investigated the ability of two diuretics, amiloride and frusemide, to prevent the development of ACTH induced hypertension in conscious sheep. Infusion of amiloride (20 mg/day) or frusemide (50 mg/day) for three days into normotensive sheep did not have any significant effects on blood pressure. Amiloride blocked ACTH-induced hypertension and the sodium retention and hypokalemia which is usually associated with ACTH administration. Frusemide failed to completely block the hypertension and potassium loss, however it blocked the transient initial urinary sodium retention associated with ACTH-induced hypertension. As frusemide failed to completely block the hypertension it is unlikely that the amiloride effect is due primarily to effects on urinary Na excretion. It is possible that amiloride is exerting its antihypertensive effects by blocking sodium channels.
Adrenocorticotropic Hormone↗
Hemodynamic effects of atrial natriuretic factor clearance receptor occupancy in conscious sheep.
The present study examined the hemodynamic actions of a non-guanylate cyclase linked or "clearance" atrial natriuretic factor (ANF) receptor ligand--des[Gln116Ser117Gly118Leu119Gly120] ANF 102-121 (C-ANF 4-23)--in conscious sheep. The effect of this peptide on the duration and potency of the hypotensive action of ANF (99-126) was also studied. C-ANF (4-23), infused at 400 micrograms/h for 2 h, reduced blood pressure, cardiac output and stroke volume, and increased total peripheral resistance slightly. These changes were similar to those previously observed with infusion of 20 micrograms/h ANF (99-126) in sheep. Endogenous ANF concentration increased from 28 +/- 13 to 85 +/- 18 pg/mL after 80 min infusion of C-ANF (4-23). The duration of hypotensive action from injection of ANF (99-126) was increased almost two-fold during infusion of C-ANF (4-23), however the hypotensive potency of ANF (99-126) was similar both prior to and during infusion of C-ANF (4-23). These studies support the concept of the metabolism of ANF via clearance receptors, suggesting that long-term hemodynamic actions of endogenous ANF may be achieved via prolonged blockade of these clearance receptors.
Animals↗
Adrenocorticotrophin-induced hypertension in the rat: haemodynamic, metabolic and morphological characteristics.
Adrenocorticotrophin (ACTH) administration has been systematically studied in man and sheep. It raises systolic blood pressure (SBP) in the rat, but this has been little studied. ACTH was injected once daily at 0.5 mg/kg for 12 days in male Sprague-Dawley rats (n = 19). Sham-injected animals were studied in parallel (n = 15). ACTH increased SBP from 94 +/- 4 to 121 +/- 4 mmHg (P less than 0.001), significantly greater (P less than 0.02) than sham injection. The SBP of ACTH-treated rats was significantly higher than that of sham-injected rats when the same animals were measured by both the tail-cuff method (ACTH, 126 +/- 3 mmHg; sham, 99 +/- 3 mmHg) and direct arterial cannulation (ACTH, 137 +/- 2 mmHg; sham, 123 +/- 3 mmHg): P less than 0.005 and P less than 0.001, respectively. There was a loss of body weight, and increased water intake and urine output in ACTH-treated animals compared with both control (P less than 0.001) and sham treatments (P less than 0.02). ACTH increased plasma [Na] (sham, 140 +/- 1 mmol/l; ACTH, 145 +/- 1 mmol/l; P less than 0.001) and urinary Na excretion compared with control (P less than 0.01) and sham injection (P less than 0.05), and also decreased plasma [K] (sham, 4.6 +/- 0.2 mmol/l; ACTH, 3.3 +/- 0.8 mmol/l; P less than 0.01) and increased urinary K excretion (P less than 0.01) compared with control. SBP in adrenalectomized animals (n = 10) was unchanged by ACTH. ACTH increased adrenal, renal, cardiac and brain weights compared with sham injection (P less than 0.05). There were no significant changes in vascular morphology, although ACTH treatment increased glomerular epithelial cell droplets and abolished the adrenal zona glomerulosa.
Adrenal Glands↗
The failure of nisoldipine to prevent the hypertensive response to cyclosporine A infusion in sheep.
Hypertension and nephrotoxicity are major clinical problems associated with cyclosporine A administration. Sheep rapidly develop hypertension after intravenous administration of cyclosporine A at 6 mg/kg per day over 5 days, and this is associated with a rise in peripheral resistance. Nephrotoxicity is not a feature of cyclosporine A-induced hypertension in this species. This study reports the use of nisoldipine to investigate the role of Ca2(+)-induced smooth muscle contraction in cyclosporine A-induced hypertension in conscious sheep. After 3 control days, nisoldipine at 24 mg/day was infused intravenously alone for 24h (E1), followed by 5 days of nisoldipine plus cyclosporine A (6 mg/kg per day; E2-E6). After 24 h of nisoldipine alone, mean arterial pressure (MAP) was unchanged, heart rate rose from a control value of 60 +/- 2 beats/min to 102 +/- 9 beats/min (P less than or equal to 0.001), calculated total peripheral resistance (CTPR) fell from 15.8 +/- 0.5 to 11.7 +/- 0.5 mmHg/l per min (P less than or equal to 0.001) and stroke volume fell from 73 +/- 4 ml/beat to 60 +/- 5 ml/beat (P less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effects of atrial natriuretic factor on pressor responsiveness to angiotensin II, norepinephrine, and vasopressin in conscious sheep.
The effects of pretreatment with atrial natriuretic factor (ANF) on the pressor responsiveness to injections of angiotensin II (ANGII), arginine vasopressin (AVP), and norepinephrine (NE), as well as the effect of pretreatment with ANGII on the hypotensive responses to ANF injection were studied in conscious sheep. The hemodynamic effects of ANF infusion (100 micrograms/h for 60 min) were also examined in animals pretreated with the angiotensin-converting enzyme (ACE) inhibitor, captopril. Infusion of ANF attenuated the pressor responsiveness to exogenous AII and NE, but caused no significant change in the blood pressure increases produced by vasopressin. In contrast, infusion of AII had no effect on the immediate hypotensive response to ANF injection. Infusion of ANF for 60 min produced similar hemodynamic actions in sheep during ACE inhibition as compared with the responses observed in normal sheep, although the reduction in cardiac output and increase in calculated total peripheral resistance was attenuated. Infusion of captopril increased plasma concentration of renin (PRC), and infusion of ANF produced no further change in PRC. In conclusion, the short-term cardiovascular responses to ANF infusion in conscious sheep are not mediated solely by inhibition of the renin-angiotensin system. However, ANF attenuates the pressor actions of pharmacologic doses of exogenous ANGII and NE. In contrast, the vasodepressor response to exogenous ANF injection was not altered in animals receiving ANGII infusion. This study suggests that ANF may be important in regulating the effects of endogenous vasoconstrictor hormones on blood pressure (BP).
Angiotensin II↗
Cyclosporine-induced hypertension in sheep. The role of thromboxanes.
Thromboxanes have been implicated in the CsA-induced hemodynamic changes and impairment in renal function in humans and in rats. We have previously shown that administration of intravenous CsA to sheep for 5 days at 12 mg/kg/day produces a hypertension that is resistance mediated and independent of nephrotoxicity. In this study we used a thromboxane synthetase inhibitor, U63,557A, to examine the role of thromboxanes in the CsA-induced hypertension in the sheep. The thromboxane synthetase inhibitor had no effect on blood pressure in normotensive sheep. Serum thromboxane levels were not elevated with CsA, and the inhibitor had a minimal effect on blood pressure during CsA treatment, suggesting that thromboxanes are not a major contributor to the rise in blood pressure seen in the sheep. A study of the dose-response relationship for CsA at 3, 6, and 24 mg/kg/day for 5 days indicated that maximal blood pressure responses were attained with 6 mg/kg/day.
Animals↗
A 'hypertensinogenic' class of steroid hormone activity in man?
1. Studies in sheep have led to the concept of a 'hypertensinogenic' (HT) steroid hormone activity, whereby the blood pressure (BP) raising effects of adrenocortical steroids can be separated from their in vivo glucocorticoid (GC) or mineralocorticoid (MC) activities. 2. The three main lines of evidence are as follows: (i) BP raising effects of ACTH cannot be reproduced by appropriate rates of infusion of steroids with GC and MC activities; (ii) certain steroids e.g. 9 alpha-fluorocortisol can increase BP at rates of infusion below threshold for in vivo GC or MC actions and for many steroids there is no correlation between GC, MC and HT effects; (iii) demonstration of differential antagonism of HT, MC and GC effects. 3. Studies in man show that the BP effects of ACTH are due to cortisol (F) at levels which have both MC and GC activity. However, BP effects of ACTH cannot be blocked by MC and GC antagonists. 4. Although complete separation of in vivo GC, MC and HT activities has not been possible in man, our own studies show a degree of dissociation. Taken together, these data suggest that steroids may raise BP by a HT mechanism distinct from classical in vivo MC or GC activities in man as well as sheep.
Administration, Oral↗
Haemodynamic effects of long-term endothelin infusion in conscious sheep.
1. Synthetic human endothelin-1 was infused intravenously at 15 micrograms/h for 24 h to examine its cardiovascular actions in five conscious sheep. 2. Endothelin produced a maximum increase in mean arterial pressure (MAP) of +8 mmHg at 8 h, with an increase in calculated total peripheral resistance (CTPR) of +2.6 mmHg/L per min, whilst cardiac output (CO) was unchanged. At 24 h MAP was not significantly elevated, however CTPR had increased by +2.8 mmHg/L per min and CO had decreased by 0.9 L/min. 3. This study shows that long-term administration of endothelin produces sustained arterial vasoconstriction in sheep.
Animals↗
Lack of pressor response to intracerebroventricular infusion of aldosterone in sheep.
1. Studies in the rat and the dog have shown that infusion of aldosterone for several weeks into the cerebral ventricles (ICV) can produce hypertension at doses that do not have an effect when infused systemically. We have previously shown that a high physiological dose of aldosterone infused intravenously at 10 micrograms/h in sheep produces an increase in blood pressure of 7 mmHg within 2 days. 2. In this paper we report the effects of ICV infusion of aldosterone at 2 micrograms/h for 6 days in conscious sheep. 3. Neither blood pressure nor heart rate were altered, and there were no consistent changes in any of the metabolic parameters measured. 4. These results do not support a role for central effects of aldosterone in the hypertension produced by systemic infusion of the steroid in sheep.
Aldosterone↗
Renal actions of atrial natriuretic factor: modulation of effect by changes in sodium status and aldosterone.
To examine the effect of changes in Na status on the renal response to atrial natriuretic factor (ANF), human ANF-(99-126) was infused into the renal artery of conscious sheep while Na replete, Na depleted, or Na loaded. The natriuretic response to ANF was attenuated during Na depletion and enhanced in Na-loaded animals. To demonstrate that the enhancement or attenuation of response was related to Na status rather than to the initial level of Na excretion, aldosterone was infused into the renal artery for 2 h to decrease Na excretion to a level inappropriately low for the animal's Na status (and not different from Na-depleted animals), and they were again challenged with ANF. Their response to ANF, however, was not significantly different from that in normal Na-replete animals but was significantly greater than that observed in Na-depleted animals. Similarly, Na-loaded animals treated with aldosterone had control Na excretion in the Na-replete range; however, their response to ANF was not significantly different from that of Na-loaded animals. The response to ANF was enhanced in sheep treated with aldosterone for 48 h, consistent with Na retention and hypervolemia, secondary to aldosterone treatment. The study demonstrates that Na status or some associated physiological parameter is an important determinant of the natriuretic response to ANF. The present series of experiments demonstrate that changes in aldosterone levels per se are not a determinant of the natriuretic response to ANF.
Aldosterone↗
Hemodynamic interactions of atrial natriuretic factor with the sympathetic nervous system in sheep.
The hemodynamic effects of short-term infusion of atrial natriuretic factor (ANF) were observed in sheep with combined alpha/beta adrenoceptor pharmacological blockade. The effect of ANF on the sympathetically-mediated baroreflex system was observed in conscious sheep in which aortic and vena caval balloon occluders had been surgically implanted. ANF infused at 100 micrograms/h for 60 min produced similar effects on blood pressure, cardiac output and stroke volume during alpha/beta-adrenoceptor blockade, compared to the responses seen in normal sheep, however the increases in heart rate and total peripheral resistance were reduced. ANF markedly enhanced the gain of the baroreceptor-heart rate reflex in the sheep. This effect may mediate the large increase in heart rate which is associated with a small fall in blood pressure during short-term infusion of ANF. In conclusion, the sympathetic nervous system plays an important role in regulating the reflex cardiovascular responses to short-term infusion of ANF in sheep. The large species variation in the hemodynamic responses to ANF may be related to differing degrees of stimulation or inhibition of the baroreceptor system to affect heart rate and/or peripheral resistance.
Adrenergic alpha-Antagonists↗