Vascular changes in DOCA hypertension. Influence of a low protein diet.

Abstract

SUMMARY The goal of this study was to characterize the influence of a low protein d iet on vascular changes induced by deoxycorticosterone acetate (DOCA) hypertension. DOCA hypertensive and control normotensive rats were placed on a low protein (5%) diet for 4 weeks. This intervention blocked the further increase in systolic blood pressure of rats treated with DOCA; systolic blood pressures of control rats were not influenced by the low protein diet. The sensitivity of isolated mesenteric arteries to norepinephrine was increased in DOCA hypertensive rats compared to that in arteries from control rats; arterial strips from rats maintained on the low protein diet were less sensitive to the catecholamine than arteries from their respective control diet group. Vascular sensitivity to calcium was identical in both normotensive and DOCA hypertensive rats, and the low protein diet had no effect on this measure of calcium activation. Calcium-induced relaxation was depressed in arteries from DOCA hypertensive rats, suggesting a decreased stabilizing influence of the cation on the excitable membrane. Arteries from rats maintained on the low protein diet showed enhanced relaxation to calcium compared to those from their respective control diet group. Membrane stores of calcium available for activation by norepinephrine were increased in arteries from DOCA hypertensive rats; the low protein diet decreased the storage capacity of these membrane sites. The total protein content of the aorta was increased in DOCA hypertensive rats and depressed to control level in DOCA rats maintained on low protein diet. No change was observed in actomyosin content nor in the aclinto-myosin ratio during the DOCA hypertension or the addition of a low protein diet. Since one action of DOCA is to increase cellular protein synthesis, the attenuation of these vascular changes in DOCA rats maintained on a protein-deficient diet is probably due to a decrease in available substrate. T HE importance of the vascular system in the pathogenesis and maintenance of hypertension has been well documented. ' 3 Both functional and structural alterations in the vasculature contribute to the development and maintenance of the increased arterial pressure. Since these vascular alterations occur in all forms of hypertension, regardless of the initiating factor, they may be considered to be the final common pathway in the pathogenesis of hypertension. 'The structural alterations are of two types. One type is a thickening of the vessel wall, due to hypertrophy of

Extracellular calcium and altered vascular responsiveness in the deoxycorticosterone acetate-salt rat.

“…This lack of change may be due to the fact that no change in the sensitivity to NE itself was observed. Moreland et al, 6 however, have observed an increase in NE responsiveness of VSM from DOCA-salt hypertensive rats, which they suggest is mediated by an increase in the membrane stores of Ca 2+ . Although the exact mechanism (or mechanisms) by which the Ca 2+ sensitivity is increased in VSM from DOCA-salt hypertensive rats cannot be determined from this study, two possible general mechanisms are suggested.…”

“…Calmodulin levels are not altered in VSM from DOCA-salt hypertensive rats, 15 and the actomyosin content and actin-to-myosin ratio remain unchanged. 6 To our knowledge, studies on other components involved in the contractile process of VSM from hypertensive animals, such as myosin light chain kinase, have not been performed.…”

“…Another aspect of altered Ca 2+ handling by the VSM in DOCA-salt hypertension is its decreased ability to stabilize the membrane. 6 Again, this could result in an enhanced responsiveness of the VSM to various stimuli.…”

“…Whereas Hinke 4 has shown an increased vasoconstrictor-sensitivity of VSM to Ca 2+ , others have shown either ho change 5 or a decreased response. 6 The present study investigated the effect of altered extracellular Ca 2+ concentration on the responsiveness of rings of femoral artery from DOCA-salt hypertensive rats to KCI depolarization and norepinephrine (NE) stimulation. In addition to the increased vasoconstrictor response, a decrease in the vasodilator responsiveness has been reported in this model of hypertension.…”

Adrenergic neurotransmission in tail arteries from two-kidney, one clip, renal hypertensive rats.

“…This response of the adrenergic nerve ending may partially explain the increased sensitivity found in this study to norepinephrine of the vascular smooth muscle in hypertension. It is proposed that the smooth muscle increases its sensitivity to the catecholamine in response to the reduced release of the transmitter from 28 that accompanies the development of hypertension results in an effective denervation of the smooth muscle cells that become increasingly farther away from their adrenergic supply at the adventitial-medial border of the blood vessel. This latter speculation is supported by the observation that the vascular cells nearest the luminal surface are more sensitive to norepinephrine whereas those nearest the external surface are less sensitive to the catecholamine.…”