Biomedical subjects

M Haass

Publications and source records attributed to M Haass.

79 records · Page 5Linked to original sources

PubMed1985

Cardiovascular effects of calcitonin gene-related peptide in the pithed rat: comparison with substance P.

Recently it has been shown that calcitonin gene-related peptide (CGRP) and substance P (SP) are coexisting in central and peripheral nerve endings of sensory neurons. In the present study we compared the vasodepressor and plasma extravasating activity of CGRP with that of SP. Systemic administration of CGRP to pithed, vagotomized rats evoked a dose dependent, long lasting vasodilation accompanied by a parallel rise in heart rate. The tachycardic response to CGRP may indicate a direct positive chronotropic action on the heart since this effect could not be blocked by beta-adrenoceptor blockade. For any equimolar dose the hypotensive effect of CGRP was much larger than that of SP. Both, CGRP and SP, showed a more pronounced decrease in mean arterial blood pressure after elevation of basal blood pressure levels by constant infusion of either phenylephrine, arginine-vasopressin, or angiotensin II. After systemic administration in equimolar doses CGRP was much less effective in producing plasma extravasation than SP. In conclusion, at equimolar doses CGRP is 10 times more potent than SP in producing vasodilatation but it possesses less than a third of the potency of equimolar doses of SP in producing plasma extravasation.

Angiotensin II↗

PubMed1985

Differential inhibition of alpha adrenoceptor-mediated pressor responses by rat atrial natriuretic peptide in the pithed rat.

Previous investigations have shown that rat atrial natriuretic peptide (r-ANP,5-28, atriopeptin III), antagonizes the effects of various pressor hormones (angiotensin II, vasopressin and norepinephrine) but is ineffective against pressor responses to acute spinal cord stimulation. Because the latter are believed to be mediated by intrajunctional alpha-1 adrenoceptors, whereas the others are thought to involve mainly extrajunctional receptors, we explored the possible specificity of r-ANP for alpha adrenoceptor subtypes, by comparing r-ANP, the calcium channel blocker nifedipine and the vasodilator sodium nitroprusside in their ability to inhibit pressor responses to the alpha-2 and alpha-1 adrenoceptor agonists, clonidine and phenylephrine, in pithed, vagotomized rats. Acute pressor responses to bolus-injected clonidine were dose-dependently attenuated by both r-ANP (up to 21%) and nifedipine (up to 37%), but acute pressor responses to phenylephrine were unaffected. Sodium nitroprusside inhibited pressor responses to clonidine (up to 67%) and phenylephrine equally (up to 66%). Pressor responses during constant infusions of clonidine and phenylephrine were attenuated similarly by r-ANP and nifedipine. This pattern of results, alpha-2 adrenoceptor specificity during immediate pressor responses but not during sustained pressor responses, suggests that r-ANP, like nifedipine, attenuates those adrenoceptor-mediated pressor responses which depend on slow transmembrane calcium fluxes.

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Characterization and presynaptic modulation of stimulation-evoked exocytotic co-release of noradrenaline and neuropeptide Y in guinea pig heart.

The relationship between noradrenaline and neuropeptide Y (NPY) release was investigated in the in situ perfused guinea pig heart with intact sympathetic innervation. For determination of NPY concentrations in the perfusate, a specific radioimmunoassay was employed and further characterized. Electrical stimulation of the left stellate ganglion (4, 8, 12, and 50 Hz; for 10 min) evoked a calcium-dependent and frequency-related overflow of noradrenaline and NPY, which was positively correlated (r = 0.83; p less than 0.001; n = 25). When two subsequent stimulations (12 Hz; each for 1 min) were performed in the same heart, addition of noradrenaline (10 microM) 5 min prior to the second stimulation reduced NPY overflow by 43 +/- 10%. The stimulated release of noradrenaline and NPY was increased by the alpha 2-adrenoceptor antagonist yohimbine (1 microM) to 170 +/- 10% and 199 +/- 26%, and attenuated by the alpha 2-adrenoceptor agonist B-HT 920 (1 microM) to 70 +/- 9% and 68 +/- 9%, respectively. The adenosine analogue cyclohexyladenosine (1 microM) significantly reduced the stimulated overflow of both noradrenaline (to 57 +/- 5%) and NPY (to 73 +/- 8%). Exogenous NPY (100 nM) attenuated the stimulated overflow of noradrenaline by 30 +/- 6%. Uptake1 blockade with desipramine (100 nM) or nisoxetine (100 nM) prior to the second stimulation significantly increased noradrenaline overflow and attenuated that of NPY; the attenuation of the stimulation-evoked overflow of NPY was abolished by yohimbine (1 microM). Our results indicate that electrical stimulation induces a calcium-dependent, exocytotic co-release of noradrenaline and NPY.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMedDate not supplied

Propranolol inhibits nonexocytotic noradrenaline release in myocardial ischemia.

Ischemic induces a nonexocytotic noradrenaline release in the heart, which leads to high and potentially harmful interstitial noradrenaline concentrations. The effect of beta-adrenoceptor antagonists on noradrenaline release in ischemia has been investigated in the present study. DL-Propranolol (1-100 mumol/l) concentration-dependently reduced noradrenaline release during 20 min of global and total ischemia in the perfused rat heart. Other beta-adrenoceptor blocking agents such as atenolol, metoprolol, and timolol (10 mumol/l each), however, did not share this effect. Moreover, both stereoisomers of propranolol were equipotent in suppression of ischemia-induced noradrenaline release, indicating a property of propranolol independent from interaction with beta-adrenoceptors. The well known local anesthetic action of propranolol was not likely to cause its inhibitory effect on ischemia-induced noradrenaline release, as lidocaine (10 mumol/l) did not affect noradrenaline overflow in ischemia. The effect of propranolol was further examined in cyanide intoxication, an experimental model of energy depletion. In this experimental setting the release of dihydroxyphenylethyleneglycol--the major neuronal metabolite of noradrenaline--served as indicator of increased axoplasmic noradrenaline levels which are present during nonexocytotic noradrenaline release. In cyanide intoxication DL-propranolol also reduced noradrenaline overflow but did not affect release of dihydroxyphenylethylene glycol. The latter finding suggests an interaction of propranolol with the neuronal membrane transport of noradrenaline. In ischemia and cyanide intoxication, transport of noradrenaline across the plasma membrane is known to be driven by the noradrenaline carrier (uptake1) working in reverse of its normal direction--from inside to outside. Consequently, inhibitors of the noradrenaline carrier like desipramine were shown to suppress nonexocytotic noradrenaline release in ischemia and cyanide intoxication.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Dual effect of nicotine on cardiac noradrenaline release during metabolic blockade.

Nicotine-induced noradrenaline was investigated in perfused guinea pig hearts subjected to metabolic blockade that was caused either by anoxia or by cyanide intoxication. Noradrenaline, neuropeptide Y, and dihydroxyphenylethyleneglycol (DOPEG) were determined in the coronary venous overflow Neuropeptide Y is a sympathetic cotransmitter of noradrenaline, and concomitant release of both transmitters indicates an exocytotic, calcium-dependent release mechanism, whereas neuropeptide Y overflow does not occur during nonexocytotic noradrenaline release. Nonexocytotic, calcium-independent noradrenaline release, however, is associated with an increase of DOPEG overflow, which is the main intraneuronal metabolite of noradrenaline formed by monoamine oxidase if oxygen is present. Anoxia per se caused a nonexocytotic release of noradrenaline starting after 10 min of anoxia and reaching peak levels at 30 min. During anoxia, nicotine (3 and 10 mumol/l) accelerated and enhanced noradrenaline overflow, i.e., the period between the onset of anoxia and the begin of noradrenaline release was shortened and peak levels were increased. Nicotine-induced noradrenaline release was accompanied by neuropeptide Y overflow. The action of nicotine was further evaluated during energy depletion caused by cyanide. As anoxia did, cyanide administration alone resulted in noradrenaline release. In accordance with a nonexocytotic mechanism and due to the presence of oxygen, this release of noradrenaline was accompanied by an increase of DOPEG. When added 10 min after the onset of energy depletion, nicotine (10 mumol/l) caused a brief but marked enhancement of exocytotic noradrenaline release, since this release was calcium-dependent and was accompanied by a significant rise of neuropeptide Y overflow. In absence of extracellular calcium to avoid exocytosis, concomitant administration of nicotine (3-100 mumol/l) and cyanide caused a concentration-dependent acceleration of both the overflow of noradrenaline and DOPEG, whereas overflow of neuropeptide Y was not increased, thus indicating a nonexocytotic release mechanism. In conclusion, the application of nicotine during myocardial energy depletion increases overflow of noradrenaline by both calcium-dependent exocytotic release and calcium-independent nonexocytotic release mechanisms.

Animals↗

PubMedDate not supplied

Arrhythmogenic dose of acetylstrophanthidin unchanged by beta-sympathomimetics in conscious dogs.

The enhanced arrhythmogenic risk of combined treatment with cardiac glycosides and beta-sympathomimetics is referred in some textbooks, but only a few detailed studies on in vivo models are available. We therefore investigated this problem in conscious dogs in an intraindividual study. We determined the dose of acetylstrophanthidin (intravenous infusion of 5 mcg/kg per min), which provoked ventricular premature beats with and without concomitant treatment with the partial beta-agonistic compounds doxaminol (3 mg/kg p.o.), prenalterol (0.4 or 1.0 mg/kg p.o.) or isoprenaline (0.31 +/- 0.100 mcg/kg per min). In some dogs a coronary artery was narrowed in order to reduce the coronary blood supply. The arrhythmogenic dose of acetylstrophanthidin was nearly the same in all the groups investigated (range from 52.1 +/- 5.66 to 59.9 +/- 3.23 mcg/kg). Whereas the arrhythmogenic dose of acetylstrophanthidin was unchanged by beta-sympathomimetics, the combination of the glycoside and each of the beta-agonistic drugs increased the contractile force more than did either single compound. We therefore conclude that the arrhythmogenic risk of the combination of glycosides and beta-sympathomimetics may be--at least in experimental models--less than has been suggested in the past.

Adrenergic beta-Agonists↗

PubMedDate not supplied

A new formalin test allowing simultaneous evaluation of cardiovascular and nociceptive responses.

The formalin test for nociception, predominantly used with rodents, is characterized by continuous pain due to tissue injury induced by formalin. In addition to the pain generated by formalin itself, the classical formalin test for nociception comprises a number of additional strong stressful events such as restraint and injury caused by needle insertion. These events have hampered its use as a model of stress employing continuous pain as a stress stimulus. We describe here a new, simple method of a subcutaneous application of formalin in conscious rats without restraint and needle insertion. Formalin or physiological saline (controls) was injected subcutaneously through a chronically implanted catheter in the region of the lower leg. In most animals, the cardiovascular and behavioural responses to subcutaneously injected formalin were biphasic. The early phase was quantitatively characterized. Formalin (2.5%, 50 microL) induced a marked increase in mean arterial pressure and heart rate. Maximal increases occurred during the first 3 min after formalin injection and were followed by a gradual decline of both cardiovascular parameters to levels higher than the preinjection baseline. Subcutaneous saline injection did not induce any changes in mean arterial pressure and heart rate. The behavioural response to formalin featured intensive licking and biting of the injection site. The behavioural response to subcutaneous saline did not differ from the spontaneous behavioural activity recorded in noninjected rats. Subcutaneously injected formalin induced an immediate increase in plasma corticotrophin (ACTH), corticosterone, noradrenaline, and adrenaline levels, and all hormones remained increased during the whole observation period (60 min). Adrenaline and noradrenaline levels in plasma were slightly, but significantly, elevated during the initial 5 min after subcutaneous saline application but returned to basal values after 15 min. The magnitude of the hormonal responses characterizes the described formalin test as a moderate stress stimulus. The complex response pattern to formalin injected through the subcutaneous catheter is brought about exclusively by pain generated by formalin-induced tissue injury. The described technique of subcutaneous formalin injection represents a new tool to study mechanisms activating brain neuronal circuits that generate the cardiovascular, endocrine, and behavioural responses of the reaction to pain.

Animals↗