42 female rats (230–260 g) made hypertensive by bilateral renal encapsulation with latex envelopes were divided into three equal groups. Two groups were administered the angiotensin-converting enzyme inhibitor captopril (SQ 14,225) in drinking water at a concentration sufficient to yield a dose of 25 and 50 mg/kg/day, respectively. The third group was untreated. A fourth group (14 rats) served as a normotensive control group. Systolic blood pressures and body weights were measured weekly during a 4-week control and an 8-week experimental period. Both doses prevented the elevation of blood pressure to the level of the untreated hypertensive controls. Blood pressure of the group receiving the higher dose of captopril was within the range of that of the normotensive control group by the end of the experiment while that of the group receiving the lower dose was between the blood pressures of untreated hypertensive and normotensive controls. Renal encapsulation resulted in failure of the rats to grow normally. Administration of captopril at either dose had no additional effect on body weight. To test whether inhibition of the angiotensin-converting enzyme occurred at the doses of captopril used, angiotensin I (200 µg/kg s.c.) and bradykinin (200 µg/kg s.c.) were administered separately and their effects on water intakes of control and captopril-treated groups tested. Captopril inhibited the drinking response to angiotensin I while increasing it in response to bradykinin. The pressor response following intravenous administration of 1.25 µg angiotensin I/kg to anesthetized rats was also studied. The groups treated with captopril had a significantly reduced response to angiotensin I compared with those of either normotensive or hypertensive groups. The results of the three tests suggest that inhibition of the angiotensin-converting enzyme occurred at both doses of captopril, with the higher dose inducing a somewhat greater inhibition. At autopsy, heart weight of the group receiving the higher dose of captopril was significantly less than that of the untreated hypertensive group, but significantly greater than that of the normotensive group. These results also suggest that captopril, at the doses used, provided significant protection against elevation of blood pressure in renal hypertensive rats.

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Chronic dietary administration of L-tryptophan (2.5 and 5.0 g/100 g food) to rats provided significant protection against the development of hypertension induced by bilateral encapsulation of the kidneys with latex envelopes. Lower doses of tryptophan (0.5 and 1.0 g/100 g food) attenuated the rate of elevation of blood pressure, but failed to maintain systolic blood pressures at levels significantly below that of untreated renal hypertensive controls. The body weight of the rats was not affected significantly by treatment with any dose of tryptophan used. Chronic treatment with tryptophan also protected against the reduced urinary concentrating ability during a 24-hour dehydration that characteristically accompanies renal encapsulation. A modest (5–8%) effect of treatment to reduce cardiac hypertrophy was also observed. The mechanism of the antihypertensive effect of tryptophan is not revealed by these studies although they rule out the possibilities that reduction in sodium intake and/or reduction in body weight may be important factors.

A length-tension relationship was established for aortic smooth muscle of rats by means of membrane depolarization with KCl. Maximal tension was developed by aortic rings when the preload initial tension was 8-9 g. Two aortic rings (4 mm thick) were removed from segments of the aorta cut 1.5 (upper) and 2.4 cm (lower) below the aortic arch. Upper rings appeared to develop a greater tension than lower rings during depolarization with KCl. However, in spite of this quantitative difference between rings from upper and lower segments of the aorta, there were no qualitative differences observed. Clonidine, an antihypertensive agent, induced a contraction in aortic smooth muscle, apparently by way of α-adrenoreceptor stimulation. Clonidine also attenuated significantly the development of active tension by norepinephrine but did not inhibit significantly the development of active tension following membrane depolarization with KCl. This suggests that there is a partial antagonism between norepinephrine and clonidine, presumably at the site of the receptors on smooth muscle, and that clonidine does not interfere with the contractile mechanism, per se.

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