The effect of long-term vasodilatation on capillary growth and performance in rabbit heart and skeletal muscle.
The long-term effect of adenosine and of a new xanthine derivative, 1-(5-oxohexyl)-3-methyl-7-propylxanthine (HWA 285) on capillary density was studied in rabbits. Doses of both agents were established in acute experiments such that they would produce a prolonged increase in coronary and skeletal muscle blood flows without significantly affecting blood pressure or cardiac output. These doses were then chronically administered (3 to 5 weeks) by continuous intravenous infusion from portable infusion pumps carried by the rabbits. Control animals were infused with saline. Long-term administration of adenosine and HWA 285 was well tolerated by the animals. In the acute experiments, adenosine (42 mumol.h-1 iv) reduced the heart rate and produced an increase in coronary blood flow (studied using 15 micrometers radioactive microspheres) and conductance of 38% and 65% respectively, with increases in skeletal muscle of 65% and 92%. Blood pressure, cardiac output and cardiac minute work were not affected. HWA 285 (57 mumol.h-1) slightly but significantly increased blood pressure, but did not affect heart rate, cardiac output or minute work. Coronary and skeletal muscle blood flow were increased by 41% and 72%, with conductance increases of 33% and 62% respectively. The number of all capillaries present was studied in the heart and skeletal muscle using histochemical staining for alkaline phosphatase. Myocardial capillary density (capillaries per mm2, means +/- SE) was 3092 +/- 97 in the adenosine infused group and 2870 +/- 153 in the HWA 285 infused group compared with 2426 +/- 93 in the controls, ie an increase of 27% (p less than 0.001) and 18% (p less than 0.02) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001835:Body Weight; D002196:Capillaries / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology*; D005260:Female; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009132:Muscles / Q000098:blood supply*; D009929:Organ Size; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014664:Vasodilation; D014970:Xanthines / Q000494:pharmacology
D014970:Xanthines; C032114:propentofylline; D000241:Adenosine