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Biomedical subjects

R E Lang

Publications and source records attributed to R E Lang.

At least 145 records · Page 8Linked to original sources
PubMed1984

Release of opioid peptides in canine hemorrhagic hypotension: effects of naloxone.

Sixteen anesthetized foxhounds were instrumented for hemodynamic measurements. The adrenolumbar vein was cannulated, and hemorrhagic hypotension (MAP = 40 mmHg for 3h) was induced by bleeding. The plasma levels of beta-endorphin (beta-END), methionine-enkephalin (M-ENK), and leucine-enkephalin (L-ENK) were determined in systemic and adrenal venous blood by specific RIA. Five dogs received an i.v. bolus of naloxone (2 mg/kg) and a subsequent naloxone infusion of 2 mg/kg per hour 1 h after onset of hypovolemia. Eleven dogs served as controls and received equivalent volumes (1 ml/kg per hour) of saline. Hemorrhage resulted in a sharp increase in plasma concentrations of all measured opioid peptides, particularly of M-ENK (26-fold) and L-ENK (24-fold) in the adrenal effluent. Systemic beta-END levels remained 3-fold increased, whereas the ENK release decreased spontaneously. Naloxone treatment inhibited the spontaneous fall of adrenal ENK release during the hypotensive phase; the ENK values remained elevated 20- to 35-fold. Reinfusion of the autologous blood resulted in a normalization of the concentrations of all peptides in both groups. These data demonstrate that hemorrhagic hypotension will cause stimulation of release of endogenous opioid peptides. The high levels of ENK in the adrenal effluent indicate that the adrenal gland is the main source of these peptides in the circulation. In addition to beta-END, the ENK have therefore to be considered as possible factors perpetuating circulatory shock.

Adrenal Glands↗
PubMed1984

Antihypertensive effect of the GABA receptor agonist muscimol in spontaneously hypertensive rats. Role of the sympathoadrenal axis.

The antihypertensive action of central GABA-ergic stimulation was investigated in conscious stroke prone spontaneously hypertensive rats. Injection of the potent GABA agonist muscimol (0.01-1 microgram) into the lateral brain ventricle (icv) lowered mean arterial blood pressure (192.1 +/- 8.4 mm Hg) dose-dependently in stroke prone spontaneously hypertensive rats with a maximal fall of -52.7 +/- 5 mm Hg lasting for about 90 minutes. This was accompanied by bradycardia and sedation. Pretreatment with atropine (2 mg/kg, ip, or 15 micrograms/kg, icv) did not significantly influence the muscimol-induced fall in mean arterial pressure. In normotensive (109.3 +/- 1.9 mm Hg) Wistar-Kyoto controls, the maximal decrease in mean arterial pressure was -12.1 +/- 1.6 mm Hg from 109.3 +/- 1.9 mm Hg, and the duration of the effect was much less than in stroke prone spontaneously hypertensive rats, Following 1 microgram muscimol, icv, plasma noradrenaline did not fall significantly in stroke prone spontaneously hypertensive and Wistar-Kyoto rats, but in stroke prone spontaneously hypertensive rats, plasma adrenaline was fully suppressed (from 118.1 +/- 24.2 to 22.8 +/- 5.7 pg/ml) throughout the depressor response. The efferent sympathetic nervous activity as directly recorded from the n. splanchnicus was similar in conscious stroke prone spontaneously hypertensive and Wistar-Kyoto rats, and was moderately reduced in both strains by 1 microgram muscimol, icv.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1984

The cardiovascular effects of neuropeptide Y (NPY).

NPY (1ng-10/micrograms) had no effect on mean arterial pressure (MAP) or heart rate (HR) when administered into the lateral brain ventricle or cisterna magna of conscious, chronically instrumented normotensive, male Wistar rats. However upon intravenous injection (0.1-5/micrograms) it produced a dose related pressor response accompanied by bradycardia. This pressor effect was not influenced by prazosin infusion (100 micrograms/kg/min). These results suggest that NPY has no direct role in central cardiovascular regulation, but peripherally is a very potent vasoconstrictor peptide.

Animals↗
PubMed1984

Differential effects of vasopressin (AVP) and oxytocin (OXT) on the baroreceptor reflex in conscious rats.

In conscious chronically instrumented, male Wistar rats the intracisternal (ic) administration of AVP (10ng) caused an increase in baroreflex sensitivity in response to both a rise and fall in blood pressure induced by intravenous phenylephrine (1/ug) and sodium nitroprusside (13/ug) respectively. Conversely a synthetic OXT analogue (Thr4 - Gly7) OXT (10ng) injected ic depressed baroreceptor reflex function. It appears that AVP and OXT are involved in the central connections of the baroreceptor reflex arc, where they may act as physiological antagonists.

Animals↗
PubMed1984

Effect of denervation on the leucine-enkephalin content of the adrenal gland of spontaneously hypertensive rats (SHRSP).

Enkephalins are known to inhibit the release of catecholamines from sympathetic nerve endings. Thus a difference in their turnover rate between SHRSP and normotensive rats (WKY) could contribute to the altered sympathetic activity in SHRSP. One week after denervation which inhibits release of leucine-enkephalin (L-ENK), but not synthesis and processing of the L-ENK precursor, L-ENK increased with the same relative extent in both strains of rats, starting from a lower basal concentration in 7 weeks old SHRSP. In adult rats there was no difference between SHRSP and WKY before and after denervation respectively. It is concluded that the lower content of L-ENK in young SHRSP is caused by an increased release.

Adrenal Glands↗
PubMed1984

Pathogenesis of hypertension in spontaneously hypertensive rats: definite evidence against a pressor role of vasopressin.

A number of experiments were performed in order to investigate the possible importance of vasopressin (AVP) in the pathogenesis of high blood pressure in spontaneously hypertensive rats of the stroke prone strain (SHRSP). Radioimmunological studies revealed reduced concentrations of AVP in the plasma and brain of SHRSP as compared to normotensive controls. Intravenous administration of an AVP pressor antagonist had no significant influence on mean arterial blood pressure, cardiac output and total peripheral resistance in SHRSP. Crossbreeding of SHRSP with rats homozygous for hypothalamic diabetes insipidus resulted in the development of a new strain of rats which show high blood pressure despite of a complete lack in AVP. These results argue strongly against a pressor role of AVP in the development or maintenance of hypertension in SHRSP.

Animals↗
PubMed1984

Peptidergic systems: effects on blood vessels.

Peptide effects on the cardiovascular system can be caused by an action within the central nervous system; by peptidergic innervation of the end-organs of blood pressure control, i.e., the kidney, blood vessels, and heart; by local generation of peptides in the peripheral tissue; and by hormonal effects of circulating peptides. In this paper, the effects of opioid peptides and neuropeptide Y on blood vessels are discussed. Both peptides are found in noradrenergic nerve endings. They either modulate the release of catecholamines by acting on a presynaptic site or exert their effects at the post-synaptic level. The peptides are not evenly distributed throughout the sympathetic nervous system; a suborganization of sympathetic innervation begins to emerge regarding a co-localization of neuropeptides with catecholamines. The differential sympathetic innervation of endorgans of blood pressure control with respect to neuropeptides may, in the future, allow for selective activation and inhibition of parts of the sympathetic nervous system. Such a suborganization of the autonomic nervous system may not only lead to a better understanding of cardiovascular disease, but also make possible the development of new drugs which interfere more selectively with the sympathetic peptidergic system.

Amino Acid Sequence↗
PubMed1984

Pharmacological interferences with the renin-angiotensin system.

The important role of the renin-angiotensin system (RAS) in the maintenance of high blood pressure in certain forms of hypertension is well established. Inhibition of the RAS has therefore been studied with the aim to develop antihypertensive agents. Pharmacologic interferences with the RAS are possible at all steps of the formation, action and degradation of angiotensin II (ANG II). Renin activity can be inhibited by peptide analogues of angiotensinogen, peptides derived from the amino terminal sequence of pro-renin, inhibitors of acid proteases (pepstatin) and by specific renin antibodies. Inhibitors of the converting enzyme also prevent the formation of ANG II. ANG II receptor blockers (saralasin) prevent the action of the effector peptide of the RAS at the target cells. While some modes of intervention are still theoretical or experimental possibilities, others, e.g. inhibition of converting enzyme, are already used clinically for antihypertensive treatment.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2- azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498): antihypertensive action and persistent inhibition of tissue converting enzyme activity in spontaneously hypertensive rats.

The antihypertensive actions of the new converting enzyme (CE) inhibitors 2-[N-[(S)-1-Ethoxycarbonyl-3-phenylpropyl] -L-alanyl]-(1S,3S,5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498) and enalapril were compared in spontaneously hypertensive rats (SHRSP), and their effects on tissue CE activity were investigated. Oral treatment with one single dose of the CE inhibitors Hoe 498 (1 mg/kg) and enalapril (30 mg/kg) in normotensive rats produced up to 24 h CE inhibition in plasma, aorta, heart and brain cortex and a 48 h inhibition of the enzyme in kidney and lung. In SHRSP, four-week oral treatment with Hoe 498 (0.1, 1, 10 mg/kg/day) and enalapril (1, 10, 30 mg/kg/day) lowered arterial blood pressure dose-dependently, with normalization of blood pressure following the respective highest dose. Plasma CE activity was inhibited during treatment with both drugs and increased or normal after drug withdrawal, while blood pressure remained decreased for 2-3 weeks post treatment. After 4 weeks of Hoe 498 (3 mg/kg/day) in SHRSP blood pressure was normalized and CE activity was markedly reduced in plasma, lung, kidney, aorta, mesenteric artery, heart, hypophysis and medulla oblongata. The CE inhibition persisted for one week in the kidney and mesenteric artery, accompanying the persistent post treatment blood pressure reduction. Our results demonstrate the strong antihypertensive potency of Hoe 498 in SHRSP and strengthen the hypothesis that CE inhibition in target tissues such as kidney and vascular wall is an important factor involved in the antihypertensive action of CE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Angiotensin biosynthesis and concentrations in brain of normotensive and hypertensive rats.

We report here on the extraction and characterization of angiotensin I (ANG I) and angiotensin II (ANG II) from the brain of rats. High pressure liquid chromatography (HPLC) with different mobile phases combined with specific radioimmunoassays (RIA) proved to be a powerful tool for peptide characterization in biological samples; (Ile5)-ANG I, (Ile5)-ANG II and (Ile5)-ANG III could clearly be identified in cerebrospinal fluid (CSF), incubated in vivo and in vitro with renin, in total brain extracts, as well as in hypothalamus (HT), medulla oblongata (MO), cerebellum (CER) and cortex (CO). Angiotensin cleaved from CSF angiotensinogen and angiotensin extracted from brain showed retention times identical to those of plasma angiotensin and synthetic standard peptides, indicating that their amino acid sequence is probably identical. ANG I and ANG II were highest in the HT and lowest in the CO. Following bilateral nephrectomy (NX) both ANG I and ANG II persisted at control levels. Young 10 week old spontaneously hypertensive rats (SHRSP) showed significantly lower ANG I and ANG II concentrations in the HT compared with Wistar Kyoto rats (WKY). Intracerebroventricular (i.c.v.) administration of the converting enzyme inhibitor captopril caused a significant increase in ANG 1 in nephrectomized SHRSP but not in WKY. These differences were not found in 40 week old SHRSP. The data show that ANG I and ANG II are synthetized in the brain of rats. The lower concentrations and the enhanced accumulation of ANG I after converting enzyme blockade in nephrectomized young SHRSP indicate an increased turnover of angiotensin in hypertensive rats.

Angiotensin I↗
PubMed1984

Sympathetic activation following central vasopressin receptor stimulation in conscious rats.

Vasopressin (AVP)-containing pathways from hypothalamic neurons have been shown to project to blood pressure controlling brain centres. This suggests that AVP neurons may be involved in central blood pressure regulation. The effects of central AVP receptor stimulation on blood pressure, heart rate and directly recorded efferent sympathetic nerve activity in the splanchnic nerve (SNA) were investigated in conscious chronically instrumented rats. Intracerebroventricular (i.c.v.) injections of AVP (1-100 ng) caused dose-dependent blood pressure increases (maximum 26.9 +/- 3.5 mmHg) together with marked rises in heart rate and SNA. More pre-treatment with the AVP receptor antagonist d(CH2)5AVP (3/micrograms i.c.v.) completely prevented the central responses to AVP. Intracarotid injection of the same AVP doses produced rises in blood pressure accompanied by drastic falls in heart rate and SNA, similar to those seen after i.v. AVP injection. Thus, stimulation of specific neuronal AVP receptors produces a characteristic haemodynamic and sympathetic response pattern with marked sympathetic nerve activation, which is clearly distinct from the responses to vascular AVP receptor stimulation. It is concluded that AVP pathways in the brain can contribute to central blood pressure control via regulation of sympathetic outflow to the periphery.

Animals↗
PubMed1983

Angiotensin synthesis in the brain and increased turnover in hypertensive rats.

The missing link in the evidence for an active endogenous renin angiotensin system in the brain has been the demonstration of local angiotensin synthesis in the central nervous system in vivo. In this report the extraction and characterization of angiotensin I and angiotensin II from the brain of rats is described. The accumulation of angiotensin I was enhanced in hypertensive rats when the conversion to angiotensin II was blocked in vivo by the converting enzyme inhibitor captopril.

Angiotensin I↗
PubMed1983

Gabaergic stimulation inhibits central actions of angiotensin II: pressor responses, drinking and release of vasopressin.

In conscious rats, intracerebroventricular (i.c.v.) treatment with the GABA agonist muscimol (1-100 ng) suppressed the pressor responses to ANG II (100 ng i.c.v.) in a dose-dependent and reversible fashion. Treatment i.c.v. with GABA (1-500 micrograms) produced a similar but shorter inhibition. Inhibition of endogenous GABA degradation with amino-oxyacetic acid (AOAA, 30 mg/kg i.p.) markedly reduced the pressor responses to ANG II (10-1000 ng i.c.v.) with a recovery period of 24 h. This inhibition was reversed by the GABA antagonist bicuculline (1 microgram i.c.v.). Muscimol (100 ng i.c.v.) did not significantly attenuate the pressor responses to i.c.v. histamine (10 micrograms). Pretreatment with muscimol (100 ng i.c.v.) drastically reduced the drinking responses to i.c.v. ANG II (500 ng) and increased the latency to drink. Muscimol also suppressed drinking induced by carbachol (50 ng i.c.v.). Muscimol (10-1000 ng i.c.v.) inhibited the ANG II (100 ng i.c.v.)-induced release of AVP from the pituitary gland with complete suppression of the response at the highest dose. Our results demonstrate that the GABAergic system exerts an inhibitory control on pathways mediating the various central actions of ANG II, which appears to be most specific for the ANG II-induced pressor responses.

Aminooxyacetic Acid↗