Prior receptor occupancy as a determinant of the pressor activity of infused angiotensin II in the rat.

Abstract

The pressor responsiveness to angiotensin II and norepinephrine was examined in rats before and during blockade of converting enzyme activity with the nonapeptide SQ 20881. Responses to angiotensin II were impaired by sodium deprivation but enhanced by sodium loading or bilateral nephrectomy. During the period of converting enzyme blockade, a twofold increase in the angiotensin II pressor response was observed in the salt-restricted rats, whereas only a small change occurred in the salt-loaded rats. Infusion of the inhibitor produced a profound fall in the blood pressure of the salt-depleted rats with a relatively minor fall in the sodium-loaded rats. Norepinephrine pressor responses were slightly potentiated in the salt-restricted rats after administration of SQ 20881, but no change occurred in the salt-loaded or the nephrectomized rats. These observations support the view that the decrease in angiotensin II pressor activity during salt deprivation is the result of a prior occupancy of receptor sites by endogenous hormone. Therefore, a change in the number or the affinity of receptors consequent to changes in sodium balance need not be postulated to explain the phenomenon. KEY WORDS pressor responsesodium depletion and loading blood pressure norepinephrine coverting enzyme blockade bilateral nephrectomy• Most studies of the renin-angiotensin system depend on measurements of the circulating levels of renin and angiotensin II. A reciprocal relationship between plasma renin activity and sodium balance has been well documented (1, 2). Thus, sodium depletion stimulates renin secretion, and sodium loading suppresses renin release. However, under circumstances of body fluid volume depletion, during which increased renin levels are found, pressor reactivity to exogenous angiotensin becomes markedly impaired (3-7). Conversely, when sodium is given in excess, especially if a mineralocorticoid is also administered, the pressor response to angiotensin infusion is enhanced (6). Thus, angiotensin pressor reactivity appears to correlate directly with sodium balance but in-

Renin-Angiotensin System Inhibition in Conscious Sodium-Depleted Dogs

“…The increased secretion of renin was evidenced in the present study by the increase in PRA and attenuated pressor responses to angiotensin injection. It has been well documented that the angiotensin pressor response correlates directly with sodium balance but inversely with PRA (34)(35)(36). This decrease in pressor activity of exogenous angiotensin during salt depletion may be the result Values are means ± SE at a preinfusion control period (C), and at 20 min during each ofthe successive saralasin infusions at rates of0.05 (1),0.5 (2), and 5.0 (3) ,ug/kg per min.…”

Angiotensin II, aldosterone and arterial pressure: a quantitative approach. Arthur C. Corcoran Memorial Lecture.

“…The data suggest that sodium depletion tends to lower arterial pressure, partially by diminishing receptor availability, 108 ' uo arteriolar smooth muscle responsiveness, 111 and plasma volume. 110 In normal subjects, but not in anephric patients, this tendency is countered by a rise in arterial plasma angiotensin II concentration.…”

“…Plotting absolute arterial pressure against angiotensin II revealed a similar but more marked parallel downward displacement of the curve for sodium-depleted anephric patients than was apparent for sodium-depleted normal subjects. Davis, 108 and Thurston and Laragh, 110 have proposed that the decreased pressor response to angiotensin II in sodium depletion is due to prior occupation of available arteriolar smooth muscle receptor sites by endogenous angiotensin II, and that it is not necessary to invoke changes in the number or affinity of receptors. However, the studies in which arterial plasma angiotensin II was measured reemphasize that receptor occupancy is not a complete explanation of either the vaso relationship between angiotensin II and blood pressure or of the subsequent changes when angiotensin is infused.…”

Pressor response to saralasin (1-sar-8-ala-angiotensin II) bolus injection in hypertensive patients.

“…A similar relationship between renin level and sustained pressor response has been demonstrated during saralasin infusion. "2 Presumably, in low renin patients more vascular receptors are unoccupied by circulating angiotensin than in normal and high renin states, so that the partial agonistic effect of a given dose of saralasin will be greater and last longer9' [26][27][28][29][30][31][32] ( figs. 2 and 3).…”