Evidence of abnormalities in corticosteroid secretion leading to volume-dependent hypertension in Milan rats.

We examined corticosteroid secretory patterns and their relation to altered salt and water metabolism in Milan hypertensive and normotensive rats. Hypertensive rats had significantly higher blood pressures, exchangeable sodium (hypertensive, 41.2 +/- 0.3 mmol.kg-1; normotensive, 38.4 +/- 0.03 mmol.kg-1, P < .001), plasma volume (hypertensive, 5.39 +/- 0.12 mL.100 g-1; normotensive, 4.84 +/- 0.10 mL.100 g-1, P < .001), and plasma concentrations of atrial natriuretic peptide (hypertensive, 38.8 +/- 4.0 pg.mL-1, normotensive, 22.4 +/- 3.1 pg.mL-1, P < .02). These features coincide with those of mineralocorticoid-induced hypertension. Adrenal venous secretory rates (picomoles per minute) of corticosterone (hypertensive, 1696 +/- 202; normotensive, 873 +/- 139), 18-hydroxycorticosterone (hypertensive, 49.7 +/- 8.3; normotensive, 25.7 +/- 3.3), and aldosterone (hypertensive, 1.16 +/- 0.17; normotensive, 0.52 +/- 0.08) were higher in the hypertensive than the normotensive strain, but that of 11-deoxycorticosterone (DOC) (hypertensive, 94.4 +/- 14.9; normotensive, 114.3 +/- 33.9) was similar in the two strains. The corticosterone-DOC, 18-hydroxycorticosterone-DOC, and aldosterone-DOC ratios were higher in the hypertensive than the normotensive strain (P < .02), but the 18-hydroxycorticosterone-corticosterone and aldosterone-18-hydroxycorticosterone ratios were not. These results indicate increased activity of the "late" aldosterone biosynthetic pathway in the hypertensive compared with the normotensive strain caused by an increased conversion rate of DOC to corticosterone. The comparison of corticosterone secretion between the two strains indicates that 11 beta-hydroxylase rather than aldosterone synthase activity is more active in the hypertensive than the normotensive rats.

Analgesic activity of floctafenine after cholecystectomy.

In a double-blind, crossover study involving 40 post-cholecystectomy patients, the analgesic activity of a new oral nonnarcotic agent, floctafenine, was compared with that of oral meperidine and oral propoxyphene. A behavioral approach to the measurement of pain relief, i.e., the measurement of pain on movement or coughing, was used in addition to the accepted subjective method. Floctafenine 200 mg was found to have analgesic activity intermediate between that of meperidine 75 mg and propoxyphene 65 mg. Patients reported the fewest side effects after floctafenine. Initial pain level was found to affect the final pain score. Effects on pain relief due to age, sex, time of the day, and carryover effects were also examined and not found to be significant.

Estrogen receptor mRNA in mineralized tissues of rainbow trout: calcium mobilization by estrogen.

RT-PCR was undertaken on total RNA extracts from bone and scales of the rainbow trout, Oncorhynchus mykiss. The rainbow trout estrogen receptor (ER)-specific primers used amplified a single product of expected size from each tissue which, using Southern blotting, strongly hybridized with a 32P-labelled rtER probe under stringent conditions. These data provide the first in vivo evidence of ER mRNA in bone and scale tissues of rainbow trout and suggest that the effects of estrogen observed in this study (increased bone mineral and decreased scale mineral contents, respectively) may be mediated directly through ER.

Arginine vasotocin binding to isolated branchial cells of the eel: effect of salinity.

Binding of 125I-labelled arginine vasotocin (AVT) was studied in isolated intact gill cells obtained from eels (Anguilla anguilla) adapted to fresh water (FW) or to sea water (SW). Experiments carried out at 20 degrees C showed maximum and stable binding beyond 10 min of incubation. Specific binding, determined by using labelled peptide in the presence or absence of an excess of unlabelled hormone, represented 30-50% of total and was reversible, with a half-time of less than 5 min. Scatchard plot analysis revealed the presence of a single population of saturable, high-affinity sites. Maximum binding capacity (Bmax: fmol AVT/10(6) cells) and dissociation constant (Kd: nM) were respectively 5.16 and 3.21 in FW and 24.25 and 1.05 in SW. Analysis of chloride cell number and size in gills and of binding characteristics of AVT revealed parallel changes with external salinity. These results are taken as evidence for the direct intervention of neurohypophysial peptides on the gill epithelium of teleost fishes.

Atrial natriuretic peptide in the eel, Anguilla anguilla L.: its cardiac distribution, receptors and actions on isolated branchial cells.

The presence of atrial natriuretic peptide (ANP) and the nature of its binding sites were studied in fresh-water (FW)- and seawater (SW)-adapted eels using a heterologous analogue, that of the rat (rANP). Rat ANP-like immunoreactivity was demonstrated in the cardiac atria and ventricles of both FW and SW eels, and electron-dense ANP-like granules were observed. The atria and ventricles of FW eels contained significantly more granules than those of SW animals and, in both types, the atria were more granular than the ventricles. Specific binding sites for rANP were demonstrated by displacement and uptake experiments using labelled rANP in dispersed eel branchial cell preparations, enriched in chloride cells. The concentration of rANP required to produce a 50% inhibition of binding in FW cells was significantly lower than that in SW cells. Scatchard analyses revealed the presence of two classes of binding site in SW eel branchial cells but only a single class of receptor in FW cells. The affinity of the FW receptor was not significantly different from that of the SW high affinity site. Rat ANP stimulated the production of cyclic GMP (cGMP) in a dose-dependent manner, and both basal and stimulated levels of cGMP were significantly greater in SW branchial cells. These studies suggest that ANP is involved in the adaptation of the euryhaline eel to differing environmental salinities; the levels of the peptide in the heart alter with changing salinity, and the nature of the receptors in the sodium chloride-transporting epithelium of the gill changes in response to the need either to eliminate or to absorb sodium chloride.

Secretory patterns of 1 alpha-hydroxycorticosterone in the isolated perifused interrenal gland of the dogfish, Scyliorhinus canicula.

An isolated in-vitro perifused interrenal gland preparation from the dogfish Scyliorhinus canicula was used to study production of quantitatively the major corticosteroid 1 alpha-hydroxycorticosterone (1 alpha-OH-B), measured by radioimmunoassay. Basal secretory rates were 877.1 +/- 145 (S.E.M.) fmol/mg per 15 min (n = 14) and the preparation remained viable for up to 22 h, as reflected in a brisk response to 10 microM cyclic AMP (cAMP) after this time. Steroid production responded in a dose-dependent manner to porcine ACTH, with 10 microM producing a maximum stimulation of 225% above the basal secretory rate. cAMP (10 microM) produced an increase of 278% above basal, while 1 microM forskolin increased basal secretory rates by 127%. [Val5]- and [Ile5]-angiotensin II (0.1 microM) increased 1 alpha-OH-B production by 120 and 372% respectively over basal secretory rates. Increasing the concentration of K+ in the perfusate from 8 mM to 12, 18, 28 and 40 mM produced a significant rise only at 28 mM. Alterations in the concentration of Na+ and osmolarity of the perifusion medium had inconsistent effects on steroid production. Increased concentrations of urea (from 360 to 720 mM) increased the basal secretory rate by 121%, whilst reducing the concentration of urea (from 360 to 90 mM) had no effect.

Influence of an enriched dietary sodium chloride regime during gestation and suckling and post-natally on the ontogeny of hypertension in the rat.

Brattleboro rats without diabetes insipidus were subjected to sodium chloride enrichment (20-fold increase in dietary salt) at various stages of their development. Salt supplementation in the adult rat produced higher systolic blood pressure (SBP), particularly in males (142 +/- 3 versus 110 +/- 3 mmHg in control. The blood pressures of females on salt-supplemented diets during pregnancy decreased from 136 +/- 1 to 121 +/- 2 mmHg, although throughout this period the blood pressures for these rats were greater than for the control pregnant rats. Pregnant females on salt-supplemented diets also showed higher sodium concentrations in the amniotic fluid compared with controls (155 +/- 3.4 versus 134.1 +/- 6.0 mmol/l). Salt supplemented lactating mothers produced milk with similar sodium concentrations to those of the controls, but the urinary sodium concentrations of pups suckling on the former were greater than in the controls. It is concluded that the suckling pups were also salt-enriched. Rats were submitted to salt-enriched regimes in utero, during suckling, post-weaning and post-pubertally, or permutations thereof. Salt supplementation post-weaning led to consistent elevation in arterial blood pressure with males being more susceptible than females. The degree of elevation was increased if the salt-supplement was present during suckling (132 +/- 1 versus 112 +/- 1 mmHg) and was greatest when the salt-supplemented regime was administered both in utero and during the post-weaning period (154 +/- 2 versus 112 +/- 1 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial natriuretic peptide in the Milan hypertensive rat and the Milan normotensive rat: plasma concentration and binding to renal glomeruli in young, adult and aged rats.

METHODS: Blood pressures were determined in Milan hypertensive (MHS) and Milan normotensive (MNS) rats at different ages. Mean blood pressure, plasma atrial natriuretic peptide (ANP) concentration and renal glomerular receptors numbers and affinities were determined in young (25-day-old), adult (60- to 80-day-old) and aged (300-day-old) rats. RESULTS: Mean blood pressures, always higher in the MHS than in the MNS rats, increased with age in both strains. Plasma ANP concentrations were similar in the young and aged rats of both strains, but were higher in the adult MHS than in the adult MNS rats. There were no quantitative differences in the ANP receptors between young and old rats of the two strains, but an increase in the maximal binding capacity was observed, in both strains, when adult rats were compared with young rats. Moreover, saturation experiments with [125I]-rat ANP revealed a downregulation of the ANP receptors in the renal glomeruli isolated from the adult MHS rats. In isolated glomeruli the cyclic GMP stimulation by ANP was similar in adult rats of both strains. CONCLUSION: Downregulation in glomeruli of MHS rats, probably involving the clearance receptors for ANP, is concluded to occur.

Angiotensin(1-7) is an antagonist at the type 1 angiotensin II receptor.

OBJECTIVE: The present study investigated the antagonism of the amino-terminal heptapeptide fragment of angiotensin II ([des-Phe8]-angiotensin II; Ang(1-7)) to angiotensin II (Ang II) both in vitro in rabbit aortae and in vivo in rats. METHODS AND RESULTS: In rabbit isolated endothelium intact aortic rings Ang(1-7) caused a concentration-related rightward displacement of the Ang II curve and depressed the maximum response to Ang II. By applying the data to a Schild plot an apparent pA2 of 5.5 was calculated. This depression of maximum response could be reversed by co-incubation of Ang(1-7) with the competitive angiotensin antagonist losartan. Ang(1-7) had no effect on the contractile responses of several other agonists. Intravenous infusion of 10 or 100 micrograms/kg per min Ang(1-7) had no effect on the resting blood pressure in the anaesthetized rat but inhibited Ang II-induced pressor responses. CONCLUSION: The present results show that Ang(1-7) is a specific non-competitive antagonist of Ang II at type 1 angiotensin II receptors.

Clearance receptors for atrial natriuretic petide in Milan hypertensive and normotensive rats.

OBJECTIVE: Renal responses of anaesthetized Milan hypertensive (MHS) and Milan normotensive (MNS) rats to des-[Glu18-Ser19-Gly20-Leu21-Gly22]r atrial natriuretic peptide-4-23 (cANP4-23) a specific ligand for atrial natriuretic petide (ANP) clearance receptors were examined. METHODS: The peptide was administered intravenously as an initial bolus injection (10 micrograms/kg body weight) followed by constant infusion (1 microgram/min per kg body weight) for 30 min. Glomerular filtration rate, urine flow, sodium excretion and mean blood pressures were measured. Using the same protocol, plasma ANP levels were determined. RESULTS: Plasma ANP levels were significantly increased in both Milan strains (from 9.5 +/- 1.8 to 23.7 +/- 3.2 fmol/ml in MHS rats and from 9.8 +/- 1.2 to 15.9 +/- 1 fmol/ml in MNS rats). This increase was significantly greater in the MHS than in the MNS rats. The cANP4-23 infusions were diuretic and natriuretic in both strains of rats but despite a greater rise in plasma ANP level, the renal response was attenuated in the MHS compared with that in the MNS rats. Furthermore, the time course differed in that the hypertensive rats had a diuresis of slower onset. During cANP4-23 infusion, the mean blood pressure decrease was greater in the MHS rats, consistent with the fact that phenylephrine-precontracted isolated MHS rat aortae were threefold more sensitive to ANP-induced relaxation than were MNS rat aortae. Displacements of [125l]-rANP by rANP and cANP4-23 in isolated renal glomeruli indicated that MHS rats have similar amounts of cANP receptors but with a higher affinity for cANP than have MNS rats. CONCLUSION: cANP4-23 infusion increased plasma ANP more in MHS than in MNS rats. Renal responses were attenuated in the MHS rat compared with those in MNS rats. These differential actions cannot be explained in terms of glomerular ANP receptor densities, although aortic ring sensitivities differ between the two strains of rat.

Analysis of the renin gene intron A tandem repeat region of Milan and Lyon hypertensive rat strains.

The region of intron A of the rat renin gene containing a unique tandemly repeated sequence was analysed in the Milan and Lyon hypertensive rat strains and their controls, and in several Sprague-Dawley rats, using an oligonucleotide probe complementary to the tandemly repeated sequence and a renin complementary DNA probe. In the Milan rats, the size of the Bgl II DNA fragment encompassing the tandem repeat region was the same in the hypertensive (MHS) and normotensive (MNS) strains. In the Lyon model, a difference of 1.1 kilobase (equivalent to about 28 copies of the 38 basepair tandem repeat sequence) was observed in the size of the Bgl II fragment of the hypertensive (LH) and normotensive (LN) strains. However, the finding that the size of the fragment in the Lyon low-blood-pressure (LL) strain was the same as that in the LH strain rather than the LN strain suggests that the difference between the two latter strains is not by itself a major cause of the blood pressure difference between them in the intron A tandem region. An analysis of Sprague-Dawley rats, from which the Lyon strains are derived, showed that at least three different renin gene alleles, two with Bgl II fragments of the same size as those seen in the Lyon strains, are randomly segregating in this population.

Time course of lithium-induced alterations in renal and endocrine function in normal and Brattleboro rats with hypothalamic diabetes insipidus.

1. A lithium chloride (1.1 g/kg) supplemented diet was given to Long Evans (LE) and Brattleboro (DI) rats to investigate its actions in the presence (LE) and absence (DI) of vasopressin. 2. During the first 24 h, Li-supplemented LE rats displayed an initial water deficit (drinking less than renal output), increased plasma antidiuretic (ADH) titres and slightly increased plasma renin activities (PRA) and plasma osmolarities. Such changes were qualitatively similar to those seen in rats fed a normal diet, but deprived of water for 24 hours. After 12 days, the Li-supplemented rats had elevated plasma ADH titres, but reduced pituitary oxytocic and antidiuretic activities. 3. The urinary losses of Na, K and Cl exceeded dietary intakes in LE rats on the introduction of the Li-supplement, and the urinary osmolarity fell by 50%. Electrolyte balances were gradually re-established, although drinking and urine production increased in parallel to reach twice the control values by day 12 of the supplement. 4. Aldosterone and corticosterone secretory rates and their peripheral plasma concentrations were unchanged both after 24 h and 28 days of the Li-supplement. 5. Li elicited no water deficit or saluresis in DI rats, and although the polyuria and polydipsia were exacerbated, urinary osmolarity did not change over the 12 day observation period. 6. Li increased Ca excretion in both rat types; after 12 days the PRA of DI but not LE animals were increased. 7. It is concluded that the overall renal actions of Li are tempered by vasopressin rather than adrenocorticosteroids.

Secretory dynamics of 1 alpha-hydroxycorticosterone in the elasmobranch fish, Scyliorhinus canicula.

Peripheral plasma concentrations, metabolic clearance rates (MCR) and blood production rates (BPR) of 1 alpha-hydroxycorticosterone (1-OH-B) were determined in female dogfish (Scyliorhinus canicula) under varying environmental conditions. The constant-infusion technique, using high specific activity tritiated 1-OH-B, was applied to measure the MCR, and BPR were derived from the product of plasma concentration and MCR at equilibrium. Urea plasma clearances and apparent BPR were assessed in a similar manner. Fish were adapted stepwise to 140, 120, 90, 80, 70, 60 and 50% normal sea water (about 1000 mosmol/l). In all cases 1-OH-B was the major corticosteroid, cortisol and corticosterone were sought but never detected. In environments of reduced osmolarity, plasma osmolarity, sodium, chloride and urea concentrations all declined, alongside increases in plasma concentrations, MCR and BPR of 1-OH-B. In fish held in environments at concentrations greater than normal sea water, plasma osmolarity, sodium, chloride and urea concentrations all increased. Plasma clearance of urea increased in fish held in environments more dilute than sea water, while it decreased in the more hyperosmotic waters. It is tentatively concluded that homeostasis of plasma composition, with particular respect to urea, is in part regulated by 1-OH-B in the dogfish.

Effects of altered dietary sodium intake on hormonal profiles in salt-sensitive hypertensive rats.

Blood pressure and selected putatively influential hormones were measured in Brattleboro rats which were without diabetes insipidus and which were subjected to various manipulations in dietary sodium intake. Rats fed a control diet from weaning to 16 weeks of age showed a slow increase in blood pressure whereas rats fed a sodium-enriched diet for the same period exhibited sustained hypertension (115 +/- 3 versus 169 +/- 5 (S.E.M.) mmHg). In animals fed a sodium-enriched diet plasma concentrations of antidiuretic hormone (ADH) were significantly increased from 55 +/- 8 to 108 +/- 5 fmol/l. Rats fed the control diet from weaning (group A) and subsequently maintained on that diet or changed to a sodium-enriched diet or sodium-deficient diet showed no differences in their blood pressure. Plasma hormone concentrations were similar in these groups, with the exception of aldosterone suppression in rats switched from control to a sodium-enriched diet (0.26 +/- 0.04 versus 0.08 +/- 0.03 nmol/l; P less than 0.001). Animals fed the sodium-enriched diet from weaning to 16 weeks of age (group b) and either maintained on that diet or changed to a control diet showed little change in their established hypertension. Transfer to the control diet was associated with increased plasma renin concentrations (PRC) (13.8 +/- 2.1 to 122.6 +/- 6.2 nmol/l) and plasma aldosterone concentrations (0.04 +/- 0.01 to 0.08 +/- 0.01 nmol/l; P less than 0.001) but corticosteroids and ADH concentrations were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Glyceryl trinitrate enhances nitric oxide mediated perfusion within the equine hoof.

Laminitis, a microvascular disease of the equine hoof leads to severe lameness. Exogenous iv 1-arginine and transdermal nitric oxide donors, such as GTN, applied to the pasterns improve lameness during acute laminitis. Near Infrared spectroscopy in an earlier study showed haemostasis and ischaemia in the hoof during acute laminitis, both were alleviated by 1-arginine. Quantitative NIRS in the present study shows that transdermal GTN increases blood flow in the equine hoof. It is concluded that glyceryl trinitrate enhances nitric oxide mediated perfusion within the equine hoof in normal and chronically laminitic horses and ponies.

Influence of captopril on fluid and electrolyte balances and adrenocortical responses during sodium deprivation in the rat.

An angiotensin I-converting enzyme inhibitor (captopril) was given by gastric lavage at a dose of 30 mg/kg body weight per day to Long-Evans rats for a 13-day period during which they received a sodium-deficient diet. This regime was preceded by a 3-day period during which measurements were made on the animals on a sodium-replete dietary intake. Control sodium-deprived rats showed increased plasma renin activities, increased peripheral aldosterone concentrations and reduced urinary sodium excretion; they maintained positive sodium balance and the zona glomerulosa of the adrenal cortex hypertrophied. Captopril-treated sodium-deprived rats failed to reduce urinary sodium excretion sufficiently and entered a period of marked and sustained negative sodium balance. Peripheral aldosterone concentrations after 12 days of sodium deprivation in the presence of captopril treatment were similar to those of sodium-replete rats. The adrenocortical zona glomerulosa of the captopril-treated rats did not increase in size and regressive changes were noted.

Endocrine and environmental influences upon plasma cortisol concentrations and plasma renin activity of the eel, Anguilla anguilla L.

The plasma concentrations of cortisol, sodium, potassium and calcium and plasma osmolarity were determined in freshwater silver eels, after intravascular injections of eel renin preparations, mammalian ACTH, mammalian angiotensin II and eel muscle extracts. Arterial blood specimens were taken before and after injection of test substances. Partially purified eel and rat renal renins gave prolonged pressor responses in intact and hypophysectomized eels and in the nephrectomized rat anaesthetized with sodium pentobarbitone. Angiotensin, but not ACTH, produced obvious pressor responses in intact and hypophysectomized eels and in eels without their corpuscles of Stannius. Hypophysectomized eels 4-8 days after operation had reduced plasma cortisol concentrations. No change in cortisol occurred in eels after removal of the corpuscles of Stannius. Eel renin preparations and ACTH gave increased concentrations of plasma cortisol 30 min after injection into hypophysectomized and intact eels. In general, the length of the renin-generated pressor response and the increased cortisol concentration were concomitant occurrences. Angiotensin injected into eels with corpuscles of Stannius removed and into hypophysectomized eels also increased cortisol levels. Control muscle extracts produced no significant changes. There were no acute changes in plasma electrolyte concentrations after the injections. Plasma renin activity measured indirectly by bioassay of angiotensin generated in vitro was more than twice as great in eels adapted to seawater than in eels in fresh water. Plasma renin activity gradually fell when eels were transferred from seawater to fresh water, and increased when the reverse transfer was carried out.

Effects of adrenalectomy and hypophysectomy on water and electrolyte metabolism in male and female rats with inherited hypothalamic diabetes insipidus (Brattleboro strain).

Observations on water and electrolyte metabolism after hypophysectomy or adrenalectomy, in male and female rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain) are confirmed and extended. The diabetic (homozygous, DI) state relative to the non-diabetic (heterozygous, non-DI) state was characterized by (1) water intake of 55-120% body weight; (2) copious urine hypo-osmotic to plasma; (3) greater excretory rates of total solute, Na, Ca and Mg; (4) similar plasma composition except that in male DI rats, K concentration was less, and in female DI rats osmolarity was higher; (5) glomerular filtration rates (GFR) were similar with close correlations between: food and water intakes, water intake and output, urinary Na and K, Na and Cl, K and Cl, and Ca and Mg; (6) both female DI and non-DI rats had lower urinary Na:K ratios and lower plasma Na concentrations than males; (7) female DI rats excreted relatively larger amounts of K and Cl, and had higher plasma Ca concentrations than other groups. Hypophysectomized DI rats had decreased water intake and urine output, decreased solute excretion, decreased loss of osmotically free water, lower excretory rates of Na, K and Cl, and increased urinary osmolarity and K concentrations. Hypophysectomized non-DI rats had increased urinary excretory rates, decreased solute excretion (by 60-70%), decreased osmotically free water absorption, decreased urinary osmolarity, Na and K concentrations, and increased excretory rates of Ca and Mg. Hypophysectomized DI and non-DI rats had increased plasma osmolarity and Na concentration. Plasma renin activities (PRA) were higher in DI than in non-DI rats with female values lower than those of males; values for both sexes of DI and non-DI rats were reduced after hypophysectomy. Adrenalectomized DI rats had about a 50% reduction in water intake, urine output and free water clearance, increased urinary concentration of electrolytes and total solute by day 4 after operation; their Na balance (dietary:urine) did not change significantly in contrast to adrenalectomized non-DI rats in which a greater percentage of dietary Na appeared in the urine. GFR was similarly reduced in adrenalectomized DI and non-DI rats. Plasma osmolarity increased in adrenalectomized male DI, decreased in female DI and non-DI, and did not change in male non-DI rats. Plasma K concentrations increased after adrenalectomy in all groups, only non-DI rats had a significantly decreased plasma Na concentration. There was no sex difference in pituitary oxytocic activity but it was consistently reduced in DI rats; there was little change after adrenalectomy in male DI and non-DI rats; but there was an increase in DI and non-DI females. Pituitaries of DI rats had no measurable ADH activity (except the inherent activity of oxytocin). Pituitary ADH values for male and female non-DI rats were similar and were unaffected by adrenalectomy.

Near infrared spectroscopy of pedal haemodynamics and oxygenation in normal and laminitic horses.

The present study applies near infrared spectroscopy (NIRS) to the haemodynamics of the pedal circulation in normal and laminitic horses. NIRS is a noninvasive technique which uses changes in light absorption at 4 wavelengths to provide information on the changes in cytochrome aa3 (cyt aa3) reduction-oxidation (redox) status, and changes in the tissue concentration of oxyhaemoglobin (O2Hb), deoxyhaemoglobin (HHb) and therefore total haemoglobin (tHb). Other studies have shown NIRS to be sensitive to changes in tissue oxygenation and perfusion in human cerebral and limb circulation. In this study, the NIRS sensor was applied to the dorsal surface of horses' hooves. Normal and laminitic animals (acute and chronic) were subjected to manoeuvres (cuff tourniquet; digital vessel occlusion at the palmar surface of the pastern; lifting of contralateral limb) predicted to change pedal haemodynamics. The procedures produced changes in pedal haemodynamics and oxygenation, which were similar to those observed in the ischaemic/reperfused human forearm. Laminitic differed from normal horses: return of HHb to baseline was slower and the change in cyt aa3 more rapid than normal in cases of chronic laminitis, taken to indicate reduced O2 stores as a result of compromised basal perfusion. In acute laminitis, baseline values did not fluctuate following any of the manoeuvres, suggesting haemostasis in the diseased hoof. NIRS is a useful noninvasive method to assess pedal vascular function in normal and laminitic horses.

Nitric oxide donors as treatment for grass induced acute laminitis in ponies.

The potential for participation of the arginine-nitric oxide system in the aetiology of acute equine laminitis has been assessed. Nitric oxide (NO), produced by the action of NO synthase (NOS) on its substrate l-arginine, relaxes vascular smooth muscle to cause vasodilation. An attenuated normal vasodilatory tone may characterise the pathogenesis of acute equine laminitis. An intravenous infusion of 10% l-arginine in 0.9% saline caused vasodilatation in the hoof of a normal pony and immediate reperfusion of laminal tissues in an acutely laminitic pony, detected noninvasively by near infrared spectroscopy (NIRS), but the amino acid had little effect on systemic blood pressure. Treatment of acute laminitis with glyceryl trinitrate applied topically to the pasterns reduced the typical 'bounding pulses' in treated limbs, reduced lameness and lowered systemic blood pressure. Nitric oxide is likely to participate in the multifactorial pathogenesis of equine laminitis.