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P Hedqvist

Publications and source records attributed to P Hedqvist.

At least 19 recordsLinked to original sources
PubMed1994

Mast cell activation induces P-selectin-dependent leukocyte rolling and adhesion in postcapillary venules in vivo.

As studied by intravital microscopy, local challenge with the mast cell secretagogue compound 48/80 was found to increase the leukocyte rolling fraction, decrease rolling velocity and induce firm leukocyte adhesion in postcapillary venules of the rat mesentery. These effects of compound 48/80 were inhibited by a monoclonal anti-P-selectin antibody, but not by combined treatment with H1 and H2 histamine-receptor antagonists. Moreover, the response to compound 48/80 was not mimicked by exogenous histamine or 5-hydroxytryptamine (5-HT). These novel findings indicate that mediator(s) other than histamine and 5-HT evoke P-selectin-dependent leukocyte rolling and thereby promote firm leukocyte adhesion in mast cell-dependent inflammation.

Animals↗
PubMed1992

Chemoattractant-induced firm adhesion of leukocytes to vascular endothelium in vivo is critically dependent on initial leukocyte rolling.

Leukocyte rolling and firm adhesion at the venular endothelium are two discrete events in the cellular inflammatory response mediated via selectin and integrin adhesion molecules, respectively. The dependency of chemoattractant-induced firm leukocyte adhesion on the preceding rolling interaction was investigated in rat mesenteric microvessels through use of intravital microscopy. Leukocyte rolling was dose-dependently inhibited by systemic treatment with the sulphated polysaccharide fucoidin. The firm leukocyte adhesion following stimulation with the chemotactic peptide fMLP was similarly inhibited when fMLP challenge was performed subsequent to inhibition of leukocyte rolling by fucoidin. Thus, based on paired observations in single venules before and after fucoidin treatment, reduced rolling leukocyte flux prior to fMLP challenge was paralleled over a wide range by a proportional decrease in fMLP-induced leukocyte adhesion. The results demonstrate quantitatively a close relationship between the extent of leukocyte rolling and the magnitude of the subsequent firm adhesion response, and, that an initial rolling interaction is a precondition for firm adhesion to occur at physiological blood flow rates in vivo.

Animals↗
PubMed1991

Nerve-induced tachykinin-mediated vasodilation in skeletal muscle is dependent on nitric oxide formation.

Nerve-induced vasodilatation was studied by intravital microscopy of the rabbit tenuissimus muscle, pretreated with pancuronium, phentolamine, and guanethidine. Nerve stimulation of the tenuissimus nerve induced a vasodilatation which was frequency and pulse duration-dependent and insensitive to atropine and propanolol but abolished by tetrodotoxin. The nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM), but not its enantiomer, D-NAME, markedly inhibited the vasodilation induced by nerve stimulation or by exogenous substance P or neurokinin A. Vasodilatation due to calcitonin gene-related peptide, prostaglandin E2 or nitroprusside was unaffected. The substance P antagonist, spantide (30 microM), significantly attenuated nerve-induced vasodilatation, in parallel with L-NAME. Our results indicate that nerve-induced vasodilatation in skeletal muscle can be attributed to the release of substance P and/or other tachykinins and that nitric oxide subsequently mediates the response to endogenous tachykinins released from nerves.

Animals↗
PubMed1991

Potent anti-inflammatory action of calcitonin gene-related peptide.

Calcitonin gene-related peptide (CGRP), but not substance P (SP), was found to inhibit edema-promoting actions of inflammatory mediators (histamine, leukotrine B4, 5-hydroxytryptamine) in vivo in the hamster cheek pouch, human skin, and rat paw. The effect of CGRP was present in the low nanomolar dose range, and it was mimicked by activation of sensory nerves with capsaicin which caused release of endogenous CGRP-like immunoreactivity (IR). The findings provide new information on the potential impact of sensory nerve activation during inflammatory processes by indicating that sensory nerves may play an anti-inflammatory role.

Adult↗
PubMed1991

Role of adenosine in functional hyperemia in skeletal muscle as indicated by pharmacological tools.

The hypothesis that adenosine mediates blood flow increments in contracting skeletal muscle was evaluated by intravital microscopy of the microcirculation in the tenuissimus muscle of anesthetized rabbits. Motor nerve stimulation elicited muscle contractions and frequency-dependent arteriolar dilatation, particularly in terminal arterioles. The pulse duration (0.05 ms) and voltage (1.5-5 V) precluded activation of vasoconstrictor fibers, as also indicated by the lack of effect of phentolamine on resting vascular tone and on the hyperemic response to nerve stimulation. The specific adenosine receptor antagonist, 1,3-dipropyl-8-p-sulfo-phenylxanthine (DPSPX; 10(-5) M), attenuated the hyperemic response to muscle contractions. The adenosine uptake inhibitor dipyridamole (10(-8)-10(-6) M) dose-dependently dilated microvessels, an effect prevented by DPSPX (10(-5) M). Moreover, dipyridamole (10(-7) M) augmented contraction-induced hyperemia. The enhancement by dipyridamole was reversed by DPSPX (10(-5) M). The effects of adenosine uptake inhibitor and antagonist were invariably more marked in terminal than in transverse arterioles, and also more pronounced at higher stimulation frequencies. Motor nerve stimulation failed to induce alterations in vascular diameters when the neuromuscular junction was blocked by pancuronium. Thus, our observations indicate that functional hyperemia after motor nerve-induced contractions of the skeletal muscle was of postjunctional origin. Apparently, activation of adenosine receptors was responsible for a part of the evoked vasodilation.

Adenosine↗
PubMed1991

Endothelin modulation of neuroeffector transmission in smooth muscle.

In a series of muscle preparations, the peptides endothelin-1 (ET-1) and endothelin-3 (ET-3) were investigated for effects on basal muscle tone, responses to transmural nerve stimulation, and release of [3H]norepinephrine or [3H]acetylcholine. ET-1 and ET-3 contracted rat vas deferens and guinea pig ileum, ET-1 being the most potent. In the guinea pig taenia coli, ET-1 induced a relaxation whereas ET-3 was almost without relaxing effect. In the rat vas deferens, ET-1 and ET-3 enhanced contractile responses to nerve stimulation, whereas the nerve-induced release of [3H]norepinephrine was inhibited by ET-1 but not by ET-3. Contractions to exogenous ATP were increased by ET-1 whereas contractions to norepinephrine were not. In the guinea pig ileum, nerve-induced contractions were inhibited by ET-1 and ET-3 as was acetylcholine release, whereas contractions to exogenous acetylcholine were enhanced by ET-1. The inhibition of nerve-induced contractions by the endothelins was not affected by treatment with 8-(p-sulfophenyl)theophylline, BW755C, or indomethacin. The relaxation by ET-1 in the guinea pig taenia coli was not affected by treatment with NG-monomethyl-L-arginine, BW755C, or indomethacin. In conclusion, ET-1 exerted a stimulatory postjunctional effect and concomitantly an inhibitory prejunctional effect on adrenergic and cholinergic neurotransmission. Also, ET-3 exerted a stimulatory postjunctional effect, whereas a prejunctional inhibitory effect of ET-3 only was evident on cholinergic neurotransmission. Blockade of the production of nitric oxide or arachidonic acid metabolites or application of an adenosine antagonist did not alter the effects of ET-1 or ET-3.

Acetylcholine↗
PubMed1990

Endothelin modulation of neuroeffector transmission in rat and guinea pig vas deferens.

The effects of endothelin-1 (human, porcine) on contractions induced by transmural nerve stimulation, exogenous ATP or noradrenaline, and on the release of [3H]noradrenaline were studied in guinea pig and rat vas deferens. Endothelin enhanced nerve-induced contractile responses, increased basal muscle tone and increased the contractile response to exogenous ATP in both guinea pig and rat vas deferens. Endothelin did not affect the contractile responses to exogenous noradrenaline. The calcium channel blocker felodipine antagonized the stimulating effects of endothelin in the rat vas deferens, whereas blockade of lipoxygenase and cyclooxygenase pathways by a combination of BW 755C and indomethacin was without effect. In rat vas deferens preparations preincubated with [3H]noradrenaline, endothelin inhibited the 3H overflow induced by transmural stimulation, although the contractile responses were enhanced by endothelin. Pretreatment with forskolin or felodipine did not abolish the endothelin inhibition of radiotracer overflow. In conclusion, endothelin can modulate adrenergic and purinergic neuroeffector transmission in both guinea pig and rat vas deferens via inhibitory prejunctional and stimulant postjunctional mechanisms. The stimulant postjunctional effect seemed to predominate in our experiments.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1990

Adenosine modulation of resting vascular tone in rabbit skeletal muscle.

The effects of adenosine and adenosine antagonists on arteriolar vessel diameters were studied in the rabbit tenuissimus muscle in situ by means of intravital microscopy. Topically applied adenosine dose-dependently dilated transverse and terminal arterioles, an effect which was competitively antagonized by alkylxanthines. Topically applied alkylxanthines per se evoked dose-dependent vasoconstriction with the same potency order as for their adenosine antagonism. Furthermore, the concentrations of alkylxanthines eliciting vasoconstriction correlated with the observed pA2 values for their adenosine antagonism. The data indicate a physiological role of adenosine, or other purines, as regulator of resting vascular tone in mammalian skeletal muscle.

Adenosine↗
PubMed1990

Endogenous nitric oxide as a modulator of rabbit skeletal muscle microcirculation in vivo.

1. Intravital microscopy of rabbit tenuissimus muscle microvasculature was used for in vivo studies of the role of endogenous nitric oxide (NO) in local vascular control. Derivatives of arginine were applied topically in order to modulate the formation of NO from L-arginine. 2. L-NG-monomethylarginine (L-NMMA) (10-100 microM), but not D-NG-monomethylarginine (D-NMMA), dose-dependently reduced microvascular diameters. The vasoconstriction induced by L-NMMA (100 microM) was prevented by pretreatment with L-arginine (1 mM) but not with D-arginine (1 mM). Intravenous infusions of L-arginine (300 mg kg-1) reversed the effect of L-NMMA (100 microM). L-Arginine or D-arginine applied topically at 1 mM per se had no effect on microvascular diameters. 3. Vasodilatation by acetylcholine (0.03-3 microM) was significantly inhibited by L-NMMA (100 microM), whereas vasodilatation by adenosine (0.1-100 microM) or sodium nitroprusside (100 nM) was not affected. 4. The hyperaemic response after tenuissimus muscle contractions induced by motor nerve stimulation was unaffected by the presence of L-NMMA (100 microM). 5. Aggregates of platelets and white blood cells were seen in venules during superfusion with L-NMMA (100 microM), but not with D-NMMA (100 microM). 6. Our results suggest that endogenous NO formed from L-arginine is a modulator of microvascular tone and platelet and white cell-vessel wall interaction in vivo. Nitric oxide does not, however, appear to play a role in the mediation of functional hyperaemia in this tissue.

Acetylcholine↗
PubMed1990

Endogenous nitric oxide as a probable modulator of pulmonary circulation and hypoxic pressor response in vivo.

The objective of this study was to investigate the role of endogenous nitric oxide, formed from L-arginine, in the regulation of pulmonary circulation in vivo, with special reference to the hypoxic pressor response. In artificially ventilated open-chest rabbits, pulmonary vascular resistance at normoxic ventilation (FIO2 = 21%) was 78 +/- 16 cmH2O ml-1 min 1000-1 (mRUL). Hypoxic ventilation (FIO2 = 10%) increased pulmonary vascular resistance to 117 +/- 17 mRUL. N omega-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased pulmonary vascular resistance at normoxic ventilation to 192 +/- 28 mRUL and during hypoxic ventilation to 462 +/- 80 mRUL. During N omega-nitro-L-arginine methylester infusion there was also an increase in mean arterial blood pressure as well as a decrease in cardiac output that was even more pronounced during hypoxic ventilation. L-arginine reversed the effect of N omega-nitro-L-arginine methylester on pulmonary vascular resistance at normoxic ventilation to 140 +/- 26 mRUL and at hypoxic ventilation to 239 +/- 42 mRUL. In spontaneously breathing closed-chest rabbits, N omega-nitro-L-arginine methylester evoked a marked decrease in arterial PO2 and increases in respiration frequency and central venous pressure, while blood pH, PCO2 and base excess remained unchanged. Taken together these findings indicate that endogenous nitric oxide, formed from L-arginine, might be a regulator of ventilation-perfusion matching at normoxic ventilation, and that nitric oxide acts as an endogenous modulator of the hypoxic pressor response.

Amino Acid Oxidoreductases↗