Angiotensin II causes vascular hypertrophy in part by a non-pressor mechanism.

Abstract

Angiotensin II, when given in low doses, raises blood pressure slowly. When tested in vitro on vascular smooth muscle cells, it has mitogenic and trophic effects; it is not known if it has these effects in vivo. Our purpose was to determine whether vascular hypertrophy develops during slow pressor infusion of angiotensin II and, if so, whether it is pressure induced. Three experiments were done in rats infused subcutaneously with angiotensin II (200 ng/kg/min) by minipump for 10-12 days. Experiment 1: Angiotensin II gradually raised systolic blood pressure (measured in the tail) from 143±2 to 208±8 mm Hg (mean±SEM), significantly suppressing plasma renin and increasing threefold (NS) plasma angiotensin II. There was no loss of peptide in the pump infusate when tested at the end of the experiment. Experiment 2: In the perfused mesenteric circulation, vasoconstrictor responses to norepinephrine, vasopressin, and KC1 were enhanced in rats given a slow pressor infusion of angiotensin II, but sensitivity of responses was not altered. This combination of changes suggests that vascular hypertrophy develops during slow pressor infusion of angiotensin II. Experiment 3: Vessel myography was done after angiotensin II infusion with and without a pressor response. Angiotensin II raised systolic blood pressure, increased heart weight, and produced myographic changes of vascular hypertrophy in the mesenteric circulation, increasing media width, media cross-sectional area, and media/lumen ratio. Hydralazine given with angiotensin II prevented the rise of pressure and the cardiac effect but not the vascular changes. Two-way analysis of variance showed that angiotensin II significantly increased media width, media cross-sectional area, and media/lumen ratio, all independent of hydralazine. Thus, although hydralazine inhibits the pressor and cardiac effects of angiotensin II, suggesting a pressor mechanism for the cardiac change, it does not inhibit structural vascular change, which suggests that at least part of the effect has a non-pressor mechanism. (Hypertension 1991;17:626-635)

Time-dependent changes in autonomic control of splanchnic vascular resistance and heart rate in ANG II-salt hypertension

“…Although we feel that an increase in SNA to the splanchnic vascular bed is the most likely explanation for the obtained results, other possibilities exist. One is that the response to ganglionic blockade is a reflection of a generalized increase in sensitivity to vasoconstrictors due to a "vascular amplifier" effect secondary to ANG II-induced vascular hypertrophy (10). Another possibility is a withdrawal of myogenic tone in response to a drop in pressure secondary to withdrawal of sympathetic tone elsewhere.…”

“…Assessment of autonomic control of MAP, heart rate (HR), and mesenteric vascular resistance (MVR) during ANG II infusion was performed by ganglionic blockade on days 1,3,5,7,10, and 13 of ANG II and compared with values obtained on the 3rd day of control and 4th day of recovery. Ganglionic blockade was achieved by intravenous administration of hexamethonium (H0879; Sigma-Aldrich, St. Louis, MO) at a dose of 20 mg/kg (23).…”

“…Mean arterial pressure (MAP), heart rate (HR), superior mesenteric artery blood flow, and mesenteric vascular resistance (MVR) were measured during 4 control days, 14 days of ANG II delivered subcutaneously (150 ng · kg Ϫ1 · min Ϫ1 ), and 4 days of recovery in conscious rats fed a HS (2% NaCl) or low-salt (LS; 0.1% NaCl) diet. Autonomic effects on MAP, HR, and MVR were assessed by acute ganglionic blockade with hexamethonium (20 mg/kg iv) on day 3 of control, days 1,3,5,7,10, and 13 of ANG II, and day 4 of recovery. MVR increased during ANG II infusion in HS and LS rats but remained elevated only in HS rats.…”

Heart rate variability (HRV) analysis in radio and TV broadcasting stations workers

“…The latter relationship is, according to some authors, disputable. The renin-angiotensis system plays a significant role in the pathogenesis of arterial hypertension, with angiotensin II acting on the blood vessels [19]. An increase in the power spectrum in the VLF band would indicate that one of the mechanisms for the increased arterial blood pressure may be connected with the influence of EMF on the renin-angiotensin system.…”

Sodium restriction prevents cardiac hypertrophy and oxidative stress in angiotensin II hypertension

“…Although blood pressure is an important determinant of cardiac mass (8), ANG II may directly increase protein synthesis and cause myocyte hypertrophy, as reported in cultured cardiac myocytes isolated from chicks (2) and neonatal rats (34). In vivo long-term administration of an initially subpressor dose of ANG II, a model that mimics the development of human hypertension, induces a gradual rise in blood pressure associated with a cardiac hypertrophy (7,14,17). However, ANG II might increase cardiac mass independently of arterial pressure.…”