Action of Angiotensin in Normal, Adrenalectomized, and Renal Hypertensive Trained Dogs

Abstract

The relationship between filtration rate (GFR) and electrolyte excretion was investigated during infusions of low doses of angiotensin II (0.02 to 2.0 µg/sq m/min) by means of repeated clearance experiments in trained normal, adrenalectomized, and chronic experimental renal hypertensive dogs. A limited number of experiments were conducted also in dogs anesthetized with pentobarbital. Parameters of BP, C_In, C_pAH, U_Na, and U_k were determined simultaneously under conditions of a moderate water diuresis. Alterations in GFR were produced by varying the dose of angiotensin, thereby allowing a study of electrolyte excretion under conditions of decreased, relatively unchanged, and increased filtered loads. The data was grouped for statistical analysis on the basis of whether the change in GFR from control was more than –5%, within ± 5%, or above +5%. Sodium excretion (U_NaV) was found to parallel the change in GFR in the three types of dogs. Potassium excretion (U_kV) showed also a relationship with GFR in the normal and hypertensive dogs but fell significantly below control in the adrenalectomized dogs when GFR remained at control levels (within ± 5%). Significant alterations in tubular sodium transport were not apparent at the low doses of angiotensin used in this study. A dampened renal vasomotor response was observed in the hypertensive dogs which was associated with a greater tendency of GFR to increase above control. It is concluded that under the conditions of this study low doses of angiotensin can produce a decrease, no change, or an increase in the excretion of sodium as a result of the drug’s action on the renal vascular bed to alter GFR.

The role of angiotensin in the canine renal vascular response to barbiturate anesthesia.

“…Whereas many agents reduced blood flow, 1 "" exceptions have been noted. For example, Schmid 18 found that barbiturate anesthesia did not reduce renal blood flow in the trained dog. Daily sodium excretion (Schmid,18 Table 1) was 124 mEq/day, about 3 times higher than in our dogs on an unrestricted intake.…”

“…"-19 -2 " Cannon et al 22 and Levitin et al 7 pointed out the potential role of anesthesia in causing the discrepant results. Conversely, Schmid 18 denied an influence of barbiturate anesthesia, not only on resting renal blood flow but on its response to angiotensin II. Again the available data on sodium excretion may resolve the dilemma.…”

“…Schmid's animals ingested 3-fold more sodium. 18 The difference between man and dog, therefore, probably reflects not species differences but rather the experimental protocols, especially sodium intake and anesthesia. The normal kidney is sufficiently sensitive to angiotensin II to respond to physiological concentrations.…”

“…i6 H0Wever, there is considerable discrepancy between reports on the sensitivity of the renovascular bed to angiotensin. 18 " 22 In man, for example, studies performed without anesthesia demonstrated a threshold response to angiotensin infused into the renal artery at doses generally below 10 ng/min," and the renal vessels were 100-fold more sensitive to angiotensin than to norepinephrine. In anesthetized animals, on the other hand, a number of studies have revealed a requirement for much higher doses of angiotensin 7 ' " " " and it has been suggested that the renal vessels are more sensitive to norepinephrine than to angiotensin."…”

Effects of Angiotensin on Plasma Electrolyte Concentrations in Rabbits and in Man

“…This assumption has been based on an absence of demonstrable changes in venous plasma electrolyte levels in studies in which they were measured (Bock, Dengler, Krecke & Reichel, 1958;Gantt & Carter, 1964;Langford & Pickering, 1965;Schmid, 1968).…”