The role of vascular protein and renin in chronic two-kidney, one clip Goldblatt hypertension.

Chronic hypertension was induced in rats by application of a clip for 17 or 20 weeks to the unilateral renal artery and leaving the contrarenal vessel intact (two-kidney one clip hypertension, 2K-1C hypertension). Some of the rats received antihypertensive treatment with phenoxybenzamine (POB). 3H-proline was injected into all rats in the 17th experimental week to observe the in vivo incorporation rates of 3H-proline into vascular non-collagenous protein and vascular collagen. Plasma renin activity (PRA) of decapitated rats was assayed in the terminal stage of the experiment. Significant differences were noted between 2K-1C hypertensive rats and sham-operated normotensive rats, the former rats having significantly higher incorporation rates of 3H-proline into non-collagenous protein (p less than 0.001) and collagen of testicular (p less than 0.05) or mesenteric artery (p less than 0.01). The 3H-proline incorporated into each fraction of vascular protein was reduced by antihypertensive treatment with POB either in sham-operated rats (p less than 0.05) or 2K-1C rats (p less than 0.001), except for the aorta and heart. Positive correlations were noted between blood pressure and incorporated 3H-proline into non-collagenous protein of testicular arteries (r = 0.78, p less than 0.001) and mesenteric arteries (r = 0.90, p less than 0.001), in all animals. Similar positive correlations were also noted between blood pressure and tritiated collagen, to lesser extents, in testicular arteries (r = 0.67, p less than 0.001) and mesenteric arteries (r = 0.73, P less than 0.001). A rapid turnover of 3H-proline incorporated into non-collagenous protein was characteristically observed in the testicular arteries, mesenteric arteries and aorta of 2K-1C hypertensive rats 3 weeks after the proline injection. Though magnitude was low, the turnover of 3H-proline was also noted in each collagen fraction of the equivalent vessels of the same hypertensive rats. PRA of 2K-1C hypertensive rats was similar to that of sham-operated normotensive rats at the 20th week. Levels of PRA of the former or the latter rats treated with POB were 2.4-fold (p less than 0.001) or 2.5-fold (p less than 0.001) higher than those of non-medicated corresponding controls. These results indicate that (1) increased synthesis of vascular non-collagenous protein as well as collagen, especially of small arteries, plays a major role for the pathogenesis of chronic hypertension in 2K-1C rats, and (2) renin does not contribute to elevation of the blood pressure in the maintenance phase of this type of experimental hypertension.