Increased effective vascular compliance and venous pooling of intravascular volume during sustained venodilation in conscious dogs.
The hemodynamic effects of the long-acting antianginal drug molsidomine were studied in 8 chronically instrumented conscious dogs by measuring the partition of the intravascular volume and the effective compliance of the total vascular bed. The blood volume of the resting dogs was varied by +/- 4 ml/kg in a cycle of blood infusion, withdrawal and reinfusion within 12 minutes. Relating the observed alterations in mean right atrial pressure to the induced changes in intravascular volume, an effective compliance of 2.9 +/- 0.4 ml. mm Hg-1 . kg -1 (mean +/- SD) was found. Heart rate, total peripheral vascular resistance and the local capacity of the distal femoral vein did not change significantly during the cycle of volume alterations. Following 0.1 mg/kg molsidomine i.v., mean right atrial pressure was lowered by 1.6 mm Hg and mean left atrial pressure by 3.4 mm Hg; the effective compliance was elevated to 4.7 +/- 0.6 ml . mm Hg-1. kg -1 (p less than 0.001), and the central blood volume was lowered from 17.8 +/- 3.1 to 14.8 +/0 3.3 ml/kg (p less than 0.01), while the total blood volume remained constant. The decline in stroke volume and the reflexly induced increase in heart rate correlated with the control heart rate. Mean arterial pressure declined from 101 +/- 7 to 91 +/- 14 mm Hg (p less than 0.05) and total peripheral vascular resistance remained unaffected. It is concluded that molsidomine exerts exerts its hypotensive effect by dilation within the vascular low-pressure system and that this dilation can be described quantitatively in conscious animals by the analysis of the total effective vascular compliance.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001808:Blood Vessels / Q000502:physiology*; D001810:Blood Volume; D003187:Compliance; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008981:Molsidomine; D009025:Morpholines / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology*; D013558:Sydnones / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014680:Veins / Q000502:physiology
D000959:Antihypertensive Agents; D009025:Morpholines; D010069:Oxadiazoles; D013558:Sydnones; D008981:Molsidomine