Biomedical subjects

S Lundin

Publications and source records attributed to S Lundin.

At least 127 records · Page 7Linked to original sources

PubMed1987

Antidiuretic antagonism and agonism of 1-deamino-pentamethylene-2-D-phenylalanine-4-isoleucine-arginine vasopressin in rats with diabetes insipidus.

Using implanted minipumps it was shown over a period of 7 days that the vasopressin antagonist, 1-deamino-pentamethylene-2-D-Phe-4-Ile-arginine vasopressin, caused increased diuresis in normal rats and reversed vasopressin- or oxytocin-induced antidiuresis in Brattleboro rats. When the antagonist was infused alone in Brattleboro rats it induced a marked antidiuretic response, indicating that the analogue also possessed agonistic properties. The agonist action could not be demonstrated in anaesthetized, hydrated normal rats. In these animals the analogue behaved as a pure antagonist. It is concluded that analogues which behave as antagonists in one test model may display agonistic properties under different experimental conditions.

Animals↗

PubMed1987

Changes in central hemodynamics during experimental septic shock in conscious rats.

This study describes the hemodynamic, metabolic, and respiratory effects of a 4-h continuous intravenous infusion of live Escherichia coli bacteria (10(9)/h) in conscious, unrestrained rats. The early response to bacterial infusion was moderate hypotension and a marked and sustained increase in heart rate and respiratory rate. During later stages of bacteria infusion a marked decrease in stroke volume and cardiac output was observed, while total peripheral resistance increased. Arterial blood gas measurements showed an early primary respiratory alkalosis, while later stages of bacteria infusion were accompanied by progressive development of metabolic acidosis. This small-sized animal shock model may be useful for further studies, particularly since conscious rats were used to avoid the influence of anesthesia upon the development of septic shock.

Animals↗

PubMed1986

Absorption of intragastrically administered DDAVP in conscious dogs.

Plasma concentrations of DDAVP were measured after intragastric administration and intravenous infusion in dogs. Oral ingestion of DDAVP led to a dose dependent increase in peak plasma concentrations as well as area under the curve (AUC). Intravenous infusion of DDAVP (0.13 pmol/l min) resulted in a mean steady-state level of 20.3 pmol/l. Elimination half-lives for oral DDAVP were 77.6 and 76.1 min for low and high doses respectively. T1/2 estimated from the ascending part of the i.v. infusion curve was 50 min. A metabolic clearance rate (MCR) of 3.9 ml/kg . min was assessed from the i.v. steady-state level.

Absorption↗

PubMed1986

Biological effect and plasma concentrations of DDAVP after intranasal and peroral administration to humans.

DDAVP was administered intranasally (20 micrograms) and perorally (100 and 200 micrograms) to 6 hydrated volunteers. Urine was collected and blood was sampled at intervals for the following 6 hr. In all experiments DDAVP induced a marked and long lasting antidiuretic response. Radioimmunoassay of DDAVP in blood samples made it possible to calculate bioavailability of DDAVP after the two forms of administration. Following intranasal application 11.3% of the dose appeared in the blood and the figures for oral administration was 0.7-1.0%. Based on analysis of the amount of DDAVP excreted in the urine the urinary clearance rate was estimated to be 0.10 ml/min/kg body wt.

Administration, Intranasal↗

PubMed1986

Oxytocin in human follicular fluid and its possible role in the ovulatory process as studied in vitro.

Oxytocin immunoreactivity was determined in follicular fluid from human follicles at different stages of development. The concentration of oxytocin was highest in pre-ovulatory follicles. The measured oxytocin was found to co-elute with synthetic oxytocin in an h.p.l.c. system. The influence of oxytocin on the incorporation of [3H]proline into isolated human follicular wall was studied in vitro. Oxytocin induced a decrease of radiolabelling in both unripe and pre-ovulatory follicles, indicating an inhibitory effect on collagen synthesis. This effect of oxytocin was not affected by indomethacin. An oxytocin analogue, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-vasotocin, did not inhibit the incorporation of [3H]proline. The pre-ovulatory augmentation of oxytocin concentration in follicular fluid might reflect a physiological role for oxytocin in the ovulatory process. This assumption is strengthened by the observation that oxytocin may influence follicular collagen metabolism in vitro and by this means participate in the regulation of follicular rupture in the human.

Adult↗

PubMed1986

Vasotocin analogues which competitively inhibit vasopressin stimulated uterine activity in healthy women.

Three analogues of posterior pituitary hormones, 1-deamino-2-D-Tyr(OEt)-4-Val-8-Orn-vasotocin(dE-VVT), 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-vasotocin(dE-TVT) and 1-deamino-2-D-Tyr(OEt)-oxytocin(dE-OXY) were compared for their inhibitory effects on vasopressin (VP)-induced uterine activity in healthy women. At menstruation, during recording of intrauterine pressure (18 recording sessions in 11 women), intravenous infusion of lysine vasopressin (LVP, 1 ng/min/kg/body weight) induced an increase of the uterine activity and dysmenorrhoea-like symptoms. Intravenous injections of all analogues (10 micrograms/kg body weight) caused relief of symptoms and inhibition of uterine activity, dE-TVT was the most effective and dE-OXY was least active. With dE-TVT almost complete inhibition of contractions was seen during the first 10 min after injection. The duration of effect was also greatest with that analogue (40-50 min). Only dE-OXY had an agonist effect on spontaneous uterine activity. Pharmacokinetic studies of intravenous dE-TVT (10 ng/kg body weight) showed that the plasma half-life was approximately 16 min and the clearance 30 l/h. The bioavailability of 100 ng/kg given intranasally was about 5.5%. Further studies are recommended.

Adult↗

PubMed1986

Plasma kinetics of DDAVP in man.

After a bolus injection, DDAVP was infused in normal volunteers over a period of 3 1/2 hours. Blood was sampled during and after the infusion and was analyzed for DDAVP using a specific RIA. The total clearance for DDAVP was 2.6 ml/min./kg b.wt., and half-life in plasma 55 min.

Adult↗

PubMed1986

In vitro intestinal transport of vasopressin and its analogues.

The intestinal transport of vasopressin and oxytocin and their analogues 1-deamino-8-D-arginine vasopressin and 1-deamino-2-tyrosine(omicron-ethyl)-oxytocin was studied in everted segments of rat jejunum. The transported peptides were identified by specific RIA methods and by quantitative high pressure liquid chromatography. Transport rates were highest for 1-deamino-8-D-arginine vasopressin and lowest for vasopressin. No transport maximum and no competitive inhibition could be demonstrated. The distribution volume of the peptides in the intestinal mucosa was found to be smaller than that of polyethylene glycol. It is concluded that peptides of this size are transferred across the intestinal mucosa by passive processes.

Animals↗

PubMed1986

Role of arginine-vasopressin for the development of hypertension following aortic constriction.

This study concerns the role of arginine-vasopressin (AVP) for the development of hypertension after constriction of the abdominal aorta proximal to the renal arteries (PAC). The PAC was applied in AVP-deficient Brattleboro (Bb) rats and the blood pressure was recorded 3 weeks later. In untreated rats, PAC did not cause hypertension. When the rats were given AVP 0.6 or 6 nmol day-1 for 2 weeks using mini-pumps, hypertension developed both proximal and distal to the constriction. The level of the hypertension was independent of the AVP dose. When the rats were given I-deamino-4-valine-8-D-arginine-vasopressin (dVDAVP) a specific antidiuretic agonist without effect on the vascular AVP receptors, hypertension did not develop. Sham-operated rats given AVP did not develop hypertension. The PAC rats treated with AVP but not with dVDAVP had an enhanced pressor response to an i.v. bolus dose of angiotensin II. It is concluded that AVP plays an important role in the development of hypertension following aortic constriction and that the action is mediated via the vascular AVP-receptors. We suggest that the presence of AVP permits the expression of other hypertensive factors, such as angiotensin II.

Angiotensin II↗

PubMed1986

Absorption of 1-deamino-8-D-arginine vasopressin from different regions of the gastrointestinal tract in rabbits.

By using a specific radioimmunoassay for 1-deamino-8-D-arginine vasopressin (DDAVP), plasma concentrations were measured in rabbit plasma at various times after intra-gastrointestinal injections. Five anatomically distinct regions were employed to administer the peptide, namely: the stomach, the duodenum, the mid-part of the ileum, the ileo-coecal junction and the mid-part of the colon. In each case immunoreactive DDAVP could be demonstrated in plasma. The highest concentrations were observed after duodenal and ileo-coecal administration. Absorption was rapid; peak levels were reached after 10-20 min.

Animals↗

PubMed1986

Pharmacokinetics in the human of a new synthetic vasopressin and oxytocin uterine antagonist.

The pharmacokinetics in the human of 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-vasotocin (dE-TVT), was studied after iv and intranasal administration in 11 subjects at 12 experiments each route. The plasma concentration of the analogue was analysed by means of an arginine vasopressin antibody, which cross-reacted with dE-TVT to 4.7%. When given intravenously as bolus injection (10 nmol/kg/body weight), the total body clearance amounted to 0.623 +/- 0.099 (SEM) l/h kg and the half-life to 16.2 +/- 2.4 min. After intranasal administration (100 nmol/kg/body weight), the bioavailability was 10.5 +/- 2.9%. Peak concentrations in plasma appeared 2-8 min after iv and 10-45 min after intranasal administration. At the end of an observation period of 2 h measurable amounts in plasma were still found in one of the iv and seven of the intranasal experiments. It is concluded that the moderately long half-life is suitable for the treatment of hospitalized patients in premature labour where promising results with intravenous infusion (50 micrograms/min) of dE-TVT have been obtained. It is still uncertain whether or not the absorption of dE-TVT is sufficient for intranasal administration to out-patients with uterine hyperactivity in late pregnancy and to patients with primary dysmenorrhoea, where significant relief of symptoms were seen after iv administration (10 micrograms/kg body weight).

Administration, Intranasal↗

PubMed1985

Use of three specific radioimmunoassays in measuring neurohypophysial hormone content and plasma concentrations of vasopressin, oxytocin and DDAVP in rats after prolonged infusion of DDAVP.

Specific radioimmunoassays (RIA) were employed for measuring plasma and neurohypophysial concentrations of oxytocin (OT) and vasopressin (AVP) after administration of 1-deamino-8-D-Arg-vasopressin (DDAVP). DDAVP concentrations were measured by a newly-developed specific RIA. Through the use of minipumps, DDAVP was infused i.p. over a period of 3 days in normally hydrated rats. Despite decreased urine production and increased urine osmolality no changes could be observed in neurohypophysial and plasma hormone concentrations.

Animals↗

PubMed1985

Effects of ageing on cardiac performance and coronary flow in spontaneously hypertensive and normotensive rats.

The aim of the present study was to assess the influence of ageing on cardiac function and coronary flow in Wistar Kyoto normotensive rats (WKY, 16 and 78 weeks of age) and spontaneously hypertensive rats (SHR) of the same age. Cardiac function was determined on isolated hearts by means of an antegrade heart perfusion technique. Left atrial pressure and peak aortic pressure could be altered independently of each other. Recordings of cardiac output and coronary flow were then obtained at both normotensive and hypertensive levels of peak aortic pressures. Peak stroke volume (SV) was reduced with age in both WKY and SHR. Peak SV determined at normotensive pressure loads became diminished with age in WKY, while it at hypertensive pressure loads showed a small decline with age, since peak SV was low as early as 16 weeks of age. The age-dependent fall in cardiac performance was greater in SHR than in WKY, due to the enhanced peak SV in 16-week-old SHR at hypertensive pressure loads. Peak SV was markedly decreased at normotensive pressure levels in both 16- and 78-week-old SHR v. age-matched WKY. Coronary flow per unit tissue declined with age both in WKY and SHR. Coronary flow was also lower in SHR compared to age-matched WKY. With ageing this elevated performance was reduced down to the same level as in 78-week-old WKY. The age-related coronary flow reduction and the consistently reduced flow in SHR indicate a structural narrowing of the coronary vascular bed, particularly in SHR.

Aging↗

PubMed1985

Development of urinary concentrating capacity in weaning rats.

This study describes the development of the capacity to concentrate urine in 10- to 40-day-old rats that were normally weaned between 16 and 18 days, breast-fed until day 20, or abruptly weaned on day 16. Urine osmolarity after 24 h dehydration was significantly lower in 10- than in 20- and in 20- than in 40-day-old rats. The most pronounced increase occurred between 16 and 20 days in the three groups. The increase in urine osmolality was paralleled by an increase of papillary Na and urea concentrations. The length of the papilla increased linearly from day 10 to 40. Serum arginine vasopressin levels were not significantly different in dehydrated 10- and 20-day-old rats. Serum corticosterone increased significantly between 10 and 20 days of age in both normally weaned and breast-fed rats. The rise was accelerated between days 16 and 18 and paralleled the rise in urinary concentrating capacity. Adrenalectomy on day 16 abolished the increases in urine osmolality and papillary Na and urea concentrations, but not the growth of the papilla between days 16 and 20. The urinary concentrating capacity could be precociously induced by treatment with betamethasone from day 10 to 17 but not from day 17 to 20. Our results indicate that the accelerated development of urine concentrating capacity at the time of weaning is independent of dietary composition and most likely modulated by glucocorticoid hormones.

Adrenalectomy↗

PubMed1985

Plasma concentrations of 1-deamino-8-D-arginine vasopressin after intragastric administration in the rat.

A sensitive and specific radioimmunoassay for 1-deamino-8-D-arginine vasopressin (DDAVP) was developed. Plasma concentrations of DDAVP after intragastric administration were determined in non-fasted rats and a dose-related increase in plasma levels was obtained. The immunoidentity of plasma DDAVP and standard was established by high performance liquid chromatography (HPLC). Correlation of biological and immunological responses of DDAVP was assessed using the antidiuretic effect in the Brattleboro (diabetes insipidus) rat.

Animals↗

PubMed1984

Hypertension and coronary heart disease: cause and consequence or associated diseases?

Numerous epidemiologic and experimental studies have shown that increased arterial pressure accelerates atherosclerotic disease including coronary heart disease. Left ventricular hypertrophy also develops along with the development of hypertension. In uncomplicated stages of hypertension, left ventricular hypertrophy may enable the heart to maintain its performance against an increased afterload. Development of coronary heart disease in hypertensive heart disease could be one of the factors that impairs cardiac function in later stages of the disease so that the function of the heart can no longer match the increased afterload. It can also be argued that atherosclerotic disease commonly contributes to an increase in systolic blood pressure. Short-term increases in arterial pressure due to angina pectoris or other stressful events may trigger permanent hypertension; this is an interesting alternative that is yet to be investigated. Thus, it is possible that a cause/consequence relationship is involved between hypertension and coronary heart disease as opposed to a simple association. Furthermore, this cause/consequence relationship could sometimes be bidirectional.

Animals↗

PubMed1984

Regulation of renal water excretion in newborn full-term infants.

UNLABELLED: The renal response to low (45 ml/kg) and high (73 ml/kg) fluid intake was studied during an 8-hour period in healthy 3-4-day-old full-term infants. 20 infants received low fluid (LF) intake and 15 infants received high fluid (HF) intake. HF significantly increased urine flow and significantly decreased urine osmolality but did not influence glomerular filtration rate measured as the clearance of creatinine. Serum arginine vasopressin (s-AVP) was not different in the LF and HF groups and did not correlate to urine osmolality. Urinary sodium excretion was significantly correlated to the diuresis. CONCLUSION: Following high fluid intake full-term infants are capable to adaptively excrete larger urine volumes and more dilute urine by mechanisms independent of AVP. S-AVP appears to relate differently to the state of hydration and to urine osmolality in infants than in adults.

Aldosterone↗

PubMed1984

Renal sympathetic activity in spontaneously hypertensive rats and normotensive controls, as studied by three different methods.

Recordings of sympathetic activity from multifibre preparations of renal nerves have produced conflicting results concerning the presence or absence of an increased sympathetic discharge in spontaneously hypertensive rat (SHR) compared to normotensive Wistar-Kyoto rats (WKY). Therefore, recordings of single fibre activity to the kidney were performed in anesthetized SHR and WKY in comparison with multifibre recordings in conscious, undisturbed rats. A new method of estimating sympathetic discharge by analyzing the variability of "cycle activity" in multifibre nerve recordings was also used. The average nerve activity in a great number of cardiac cycles was then expressed in relation (in per cent) to the nerve activity in a small number of cardiac cycles with the highest and lowest nerve activity in each rat. Single fibre recordings showed a significantly higher sympathetic activity to the kidneys in SHR (3.8 +/- 0.3 Hz) than in WKY (1.7 +/- 0.2 Hz; p less than 0.001). Also average "cycle activity" was significantly higher in conscious SHR (34 +/- 1%) than in WKY (26 +/- 2%, p less than 0.01). This was due to the larger number of cardiac cycles in SHR with high sympathetic activity while WKY showed more of "silent" cardiac cycles which lacked nerve impulses. Further, the recordings of rectified multifibre renal nerve activity also showed an elevated sympathetic activity in conscious SHR rats. The increased renal sympathetic activity appears to reflect the "primary" central nervous "hyperreactivity" characterizing SHR hypertension. It is suggested that the increased renal sympathetic activity may be of particular importance for the development of primary hypertension in SHR and perhaps also in man.

Animals↗