Changes in noradrenaline sensitivity and morphology of arterial resistance vessels during development of high blood pressure in spontaneously hypertensive rats.

SUMMARY We have investigated whether differences seen in the pharmacological and morphological properties of mesenteric resistance vessels from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) controls are also present in vessels from young SHR and WKY rats in which there is little difference in blood pressure (BP). Segments of small arteries (lumen diameter 150 $m) were taken from a specific location in the mesenteric bed of 6-, 12-, and 24-week-old SHR and WKY rats, and mounted on a myograph capable of directly measuring their tension. Vessels were set to internal circumference L, = 0.8 Lin where Ll00 was an estimate of the internal circumference the vessels would have had when relaxed in situ and under a transmural pressure of 100 mm Hg. At all ages, compared with WKY vessels, the effective lumen diameter, I, = L,/x, was smaller in the SHR vessels. However, media hypertrophy was seen only in vessels from 12- and 24-week-old SHRs. In physiological salt solution the noradrenaline sensitivity of all vessels was similar (EDM * 2.4 nM). However, inhibition of neuronal uptake with cocaine revealed that at all ages the noradrenaline sensitivity of the vascular smooth muscle cells in the SHR vessels was greater than that of the cells in the WKY vessels. The results also suggested that the neuronal noradrenaline uptake was greater in the SHR vessels at all ages. The main increase in BP in the SHRs occurred between the ages of 6 week and 12 weeks. The results are therefore consistent with the hypothesis that differences in the structure of the resistance vessels are among the factors responsible for the development and maintenance of genetic hypertension. However, they point also to the possible involvement of differences in the noradrenaline sensitivity of the smooth muscle cells in the resistance vessel wails.