Altered Ion Transport in Vascular Smooth Muscle from Spontaneously Hypertensive Rats

Abstract

The interaction of vascular electrolytes and early spontaneous hypertension was studied in the rat aorta. Chemical composition (FLO, Na, K, Ca, Mg, Cl, collagen, and elastin), extracellular space, and cell water content were little changed. Only uronic acid and hexosaTnine contents were significantly elevated in the spontaneously hypertensive rat. Approximately 37% of the aortic weight was cellular. Functional changes in ion transport were observed in smooth muscle from hypertensive rats; the muscle exhibited decreased ability to accumulate K and extrude Na and increased turnover of -K exchange after adrenalectomy and reserpinization. The bioregulants, aldosterone, norepinephrine, and angiotensin had important actions on ion exchange. After adrenalectomy, aldosterone therapy reduced 4 -K exchange toward intact levels. Norepinephrine increased the rate of 42 K exchange with the dose-response relation having a lower median effective dose (ED S0 ) for spontaneously hypertensive rats (10-° g/ml) than it did for normal Wistar rats (2 X 10-" g/ml). Angiotensin also increased 42 K exchange with similar dose-response relations for both groups. I concluded that functional alterations observed in spontaneously hypertensive rats probably resulted from primary changes in ion transport by vascular smooth muscle rather than from secondary effects of altered regulatory systems. The decreased selectivity to K over Na and the increased turnover of ions could lead to increased reactivity to norepinephrine through effects on membrane potentials. This work was supported in part by U. S. Public Health Service Grants HE 07762 and HL 15852 from the National Heart and Lung Institute. KEYA preliminary report has appeared in abstract form (Fed Proc 31: 1020, 1972. Received April 4, 1973. Accepted for publication September 6, 1973. become available as a model for essential hypertension (3), but little change in the water, sodium, or potassium content of aortas from these rats has been observed during the early hypertensive phase (13 weeks old) (4). This observation raises the question of the role of vascular electrolyte metabolism in the pathogenesis of spontaneous hypertension and perhaps of other types of the disease.The objective of the present study was to reappraise the interaction of vascular electrolytes and spontaneous hypertension. Since ion transport by smooth muscle is especially important for regulating total wall contents (5, 6), the experimental approaches investigated functional properties as well as total wall composition. The influences of bioregulants were also studied to clarify points regarding hyperreactivity and to separate primary

Sodium pump activity in arteries of Dahl salt-sensitive rats.

“…In the S rats, increased [Rb + ] t and also increased membrane permeability, 21 if it is present in this form of hypertension, would tend to raise backdiffusion. We would expect that increased backdiffusion would reduce the net uptake.…”

Increased barium influx and potassium current in stroke-prone spontaneously hypertensive rats.

“…in hypertensive animals and humans with essential hypertension. 13 Thus, abnormal ionic permeability is thought to be a primary defect in hypertension and may contribute to the increased sensitivity to vasoconstrictors observed in vessels from hypertensive animals. 13 Calcium plays a crucial role in regulating the contractile state of vascular smooth muscles.…”

“…13 Thus, abnormal ionic permeability is thought to be a primary defect in hypertension and may contribute to the increased sensitivity to vasoconstrictors observed in vessels from hypertensive animals. 13 Calcium plays a crucial role in regulating the contractile state of vascular smooth muscles. Increased membrane permeability to Ca 2+ in hypertension could cause an increase in average myoplasmic Ca 2+ concentration (Ca 2^) and thus an increase in tension and total peripheral resistance.…”

An approach to the explanation of cell membrane alteration in primary hypertension.

“…The first studies revealing alterations in membrane transport of K + and CT were obtained by Jones 6 in smooth muscle cells of the aorta in spontaneously hypertensive rats (SHR); later signs of alteration of calcium handling were revealed in those cells and in cardiomyocytes of SHR by Aoki et al 7 and almost simultaneously by Shibata et al 8 and Wei et al 9 These data by themselves were insufficient to give any assurance of the primary character of these changes with respect to elevated blood pressure, as the data were obtained in cells subjected to functional overload. It should be pointed out also that these studies were strictly limited to vascular smooth muscles and cardiomyocytes, which was not accidental, as it reflected the traditional view (i.e., causally relating hypertension to local alterations of the cardiovascular effector cells themselves).…”