Role of prostacyclin and nitric oxide in regulation of basal microvascular hydraulic permeability in cat skeletal muscle.
The effects of prostacyclin, nitric oxide (NO) and beta2-receptor stimulation on capillary filtration coefficient (CFC) and vascular tone were analyzed in an autoperfused cat skeletal muscle in vivo preparation, to evaluate if these substances are involved in regulation of basal microvascular hydraulic permeability. CFC was increased from control (100%) to 124% with the prostacyclin-synthase inhibitor tranylcypromine and restored by simultaneous infusion of prostacyclin at 0.1 ng.kg-1. min-1, with further reduction to 76% at 1 ng. kg-1.min-1. Prostacyclin at these doses did not influence vascular tone. NO inhibition by L-NAME increased CFC to 116% of control, with a vascular resistance increase of 45%. CFC was restored by simultaneous infusion of the NO precursor L-arginine. L-arginine given alone reduced CFC to 86% of control. Tranylcypromine and L-NAME given together increased CFC to 141% of control and CFC was reduced to 86% by prostacyclin at 1 ng.kg-1. min-1 with no significant further reduction by adding L-arginine. Adrenaline alone, in a vasodilating dose verifying beta2 stimulation, or when followed by simultaneous beta-blockade with propranolol, did not influence CFC. We conclude that NO and especially prostacyclin are involved in bi-directional regulation of basal microvascular hydraulic permeability and can account for up to 30-40% increase or decrease from a basal value. Physiological beta2 stimulation has no effect on basal hydraulic permeability. The permeability-reducing effects of prostacyclin and NO are additive. NO, but not prostacyclin, is involved in regulation of basal vascular tone.
Department of Physiological Sciences, University and University Hospital of Lund, Sweden. Alma.Moller@mphy.lu.se
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002415:Cats; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000502:physiology*; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors; D008833:Microcirculation / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D014191:Tranylcypromine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D014191:Tranylcypromine; D003577:Cytochrome P-450 Enzyme System; D011433:Propranolol; D011464:Epoprostenol; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D019331:NG-Nitroarginine Methyl Ester; D004837:Epinephrine