The effect of long-term vasodilatation on capillary growth and performance in rabbit heart and skeletal muscle

Abstract

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)

Nicorandil Promotes Myocardial Capillary and Arteriolar Growth in the Failing Heart of Dahl Salt-Sensitive Hypertensive Rats

“…Long-term treatment of rabbits with vasodilators such as adenosine and a xanthine derivative in doses that markedly increase coronary and muscle blood flow results in an increase in capillary density in heart and skeletal muscle. 23 An increase in blood flow may enhance vascular growth through increases in shear stress, wall tension, or stretch. 13,24 Nicorandil induces vasodilation by opening K ATP channels and through its nitrate-like action.…”

Roles for host and tumor angiotensin II type 1 receptor in tumor growth and tumor-associated angiogenesis

“…38,39 Quantitation of Microvessels Microvessel density in the most intensive neovascularization areas (hot spots) was assessed as a parameter of tumor-associated angiogenesis according to the established methods described previously. 25,40 Briefly, the areas of highest neovascularization were found by scanning the tumors at low Tumor AT1 receptor and tumor growth N Imai et al power (  100 magnification). After the most vascularized area was identified, the individual microvessels were then counted in three different fields of an area magnified at  200 in each tissue.…”

Tissue Inhibition of Angiotensin-Converting Enzyme Activity Stimulates Angiogenesis In Vivo

“…Tissue sections snap-frozen in liquid nitrogen were stained for alkaline phosphatase to detect capillary ECs as previously described. 16,18 Capillaries in 21 randomly selected fields were counted under a ϫ10 objective to determine capillary density.…”