Increased aortic DNA synthesis precedes renal hypertension in rats. An obligatory step?

Abstract

SUMMARY The rate of DNA synthesis was determined in rats with developing and established twokidney, one clip renal hypertension. Rate of DNA synthesis was measured as [3 H]thymidine incorporation into DNA per hour. After stenosis of the renal artery, blood pressure increased over a 2-week period. Five days after clipping, there was an increase in the rate of aortic DNA synthesis before an increase in blood pressure was detected, whereas there was no DNA effect in sham-operated animals. This difference in [ 3 H]thymidine incorporation into aortic DNA could not be accounted for by alterations in thymidine pool sizes. The increase in DNA synthesis was still present 3 weeks after renal artery stenosis, although by that time blood pressure had plateaued. The role of DNA synthesis in the development of renal hypertension was investigated by determining whether inhibition of DNA synthesis with cytosine arabinoside could prevent the increase in blood pressure. Treatment of clipped rats with cytosine arabinoside for 5 days delayed the increase in blood pressure for more than 4 days, as compared with the effect of saline treatment in clipped rats. Although the possibility remains that some effect of cytosine arabinoside other than its effect on DNA synthesis could have influenced blood pressure, there were no differences in body weight, food intake, water intake, or urine output between cytosine arabinoside-treated and saline-treated rats with renal artery clips, and cytosine arabinoside treatment had no effect on blood pressure or body weight in normal rats. These results suggest that an increase in DNA synthesis may be an obligatory step in the genesis of renal hypertension. (Hypertension 8: 754-761, 1986) KEY WORDS • two-kidney, one clip renal hypertension muscle • cytosine arabinoside DNA synthesis * vascular smooth A LTHOUGH the pathogenesis of most clinical / \ cases of arterial hypertension is unknown, X \ . some of the sequelae are always the same. Patients exhibit a marked thickening of the arteries and resistance vessels 1 and a hyperreactivity to pressor agents. 23 The same types of changes have been observed in animal models of hypertension and are characterized by increases in the size and number of arterial

Aortic hypertrophy and "waterlogging" in the development of coarctation hypertension.

“…Thus, hypertrophy may appear even before the arterial pressure is significantly elevated. These results parallel the observations of others, indicating impaired maximal vasodilatation 13 and increases in aortic uptake of [ 3 H]thymidine in early 14 or even in prehypertensive stages 4 of hypertension. The present studies also provide evidence that this hypertrophic restructuring of the cardiovascular system requires approximately 10-14 days for completion, as has previously been suggested by Lundgren et al, 13 reflecting rapid normalization of wall stress.…”

“…1 -2 However, hemodynamic studies indicate increases in arteriolar wall-to-lumen ratio after only 2-3 days of one-kidney, one clip hypertension in rats, 3 and aortic [ 3 H]thymidine uptake is increased in the prehypertensive stages of murine two-kidney, one clip hypertension. 4 These observations suggest that vascular structural changes contribute to the elevated resistance even in very early stages of hypertension and that they may not be entirely pressure related. Thus, the mechanisms and roles of vascular structural changes during the development of hypertension require further study.…”

New perspectives in hypertension research. Potentials of vascular biology.

“…Consistent with this, the SHR vessel wall has been reported to undergo alterations before the development of hypertension. 93 ' 94 To date, no studies of AT! versus AT 2 receptor expression in hypertensive blood vessels have been reported.…”

Oncogènes et hypertension artérielle

“…Les cellules musculaires lisses qui y sont contenues sécrètent en effet en quantité exagérée les pro téines constituant la matrice extracel lulaire ; elles sont elles-mêmes hyper trophiées et, au moins dans les artères musculaires, hyperplasi ques [3]. Ces lésions anatomiques de l'hyper tension artérielle (HTA) en consti tuent un élément pathogénique important car elles contribuent gran dement à augmenter les résistances vasculaires et ne sont pas la seule conséquence de l'augmentation de pression : leur apparition accom pagne l'élévation tensionnelle et leur blocage la retarde [4,5] (Ba udouin-Legros M, Guicheney P, Meyer P. Am J Hypertension, sous presse).…”