1. In the isolated rat kidney, perfused at constant pressure with a medium free from renin substrate, addition of angiotensin I to the perfusate decreases renal 'plasma' flow.2. A peptide inhibitor, SQ 20881, of converting enzyme reduces the vasoconstrictor effect of angiotensin I up to a maximum of 87%, the degree of inhibition being dose-dependent.3. The molar ratio of equi-effective doses of angiotensin I and angiotensin I1 was 50 : l ' , indkating a low rate of intrarenal conversion of the decapeptide..4. The vasoconstrictor effect elicited by the addition of renin substrate to the perfusate was not inhibited by SQ 20881, even if the concentration was fifteen times that which produced the maximum inhibition of conversion of angiotensin I..

The effects on blood pressure of an antiserum against pure human kidney renin were studied in conscious and anesthetized (pentobarbital, 24 mg X kg-1 i.p.) small new world monkeys (common marmosets). The antiserum inhibited the enzymatic activity of renin by 50% in a dilution of 1:45,000 in marmoset and 1:50,000 in human plasma. The antiserum (0.2 ml i.v.) decreased blood pressure in conscious marmosets on normal sodium intake by 15 +/- 5 (SD) mmHg and after salt depletion by 31 +/- 13 mmHg. A converting enzyme inhibitor (teprotide, 2 mg X kg-1 i.v.) induced a comparable fall in blood pressure: -16 +/- 10 and -30 +/- 10 mmHg, respectively. Similar effects were observed on blood pressure of anesthetized marmosets. The correlation between pretreatment plasma renin concentration and the maximum fall in blood pressure was significant and identical for the experiments with antiserum and teprotide. These results demonstrate that antisera against human renin can be used for the specific blockade of the renin-angiotensin system in primates. In normotensive marmosets the renin-angiotensin system participates in the maintenance of blood pressure, to a degree depending on the state of sodium balance.

To determine whether vasopressin plays a role in central neural control of cardiovascular function by acting on the locus coeruleus we monitored arterial pressure and heart rate responses to graded injections of vasopressin (1-30 ng, 0.1-0.3 microliter) in the locus coeruleus of conscious, restrained rats. Cannulas were stereotaxically implanted in the locus coeruleus 2-5 days prior to experiment. Injections of vasopressin into the locus coeruleus produced dose-related increases in mean arterial pressure (12 +/- 2 to 57 +/- 6 mmHg) and heart rate (27 +/- 6 to 123 +/- 16 beats/min), which lasted over 1 h at the highest dose. Injection of the antipressor vasopressin antagonist d(CH2)5Tyr(Me) arginine vasopressin (10 ng) into the locus coeruleus blocked the cardiovascular responses to vasopressin. Administration of vasopressin into an area lateral to the locus coeruleus had no effect on mean arterial pressure but produced an increase in heart rate. Equivalent doses of saline, angiotensin II, and norepinephrine (NE) had minimal or opposite (NE) effects on arterial pressure and heart rate. Peripheral alpha-adrenergic blockade with phentolamine and beta-adrenergic blockade with propranolol blocked the cardiovascular responses to injection of vasopressin in the locus coeruleus. These results suggest that vasopressin may act in the region of the locus coeruleus to exert a central action on the cardiovascular system that is mediated by a stimulation of sympathetic outflow.

The influence of the product of the renin-angiotensinogen reaction, the des-angiotensin I-substrate (des-AI-substrate) on the renin-angiotensinogen reaction has been studied. Des-AI-substrate was prepared from purified rat angiotensinogen by reaction with immobilized renin. The des-AI-substrate had no inhibitory effect on the reaction of partially purified rat renin with rat angiotensinogen at concentrations corresponding to 0.225 or 0.45 micrometer angiotensinogen.

1. Isolated rat kidneys were perfused at a constant pressure of 90 mmHg in a single-pass system with either a cell-free medium or a suspension of washed bovine red blood cells, free of the components of the renin-angiotensin system. In red blood cell perfused kidneys renal haemodynamics and sodium reabsorption corresponded closer to values observed in the intact rat than in cell-free perfused kidneys. 2. In red blood cell-perfused kidneys in the absence of plasma renin substrate autoregulation of renal blood flow was almost complete at pressures above 90 mmHg, provided that perfusion pressure was changed rapidly. 3. Renin release varied inversely with perfusion pressure within a pressure range from 50 to 150 mmHg; the greatest changes of renin release occurred, when perfusion pressure was reduced from 90 to 70 mmHg; maximal stimulation of renin release was observed at 50 mmHg. After reduction of perfusion pressure, renin release immediately started to rise and reached a new level within 5 min. Local reduction of perfusion pressure in small arteries and arterioles by the injection of microspheres induced a short-lasting decrease in renal plasma flow and a transient stimulation of renin release. 4. High concentrations of furosemide stimulated renin release by a direct intrarenal mechanism. 5. Isoproterenol stimulated renin release in low concentrations without a concomitant vasodilation, whereas high concentrations induced an increase in both renal plasma flow and renin release. The effects of isoproterenol were completely blocked by propranolol. 6. Sodium nitroprusside induced similar increases in renal plasma flow, as did high concentrations of isoproterenol, but only a small and slow increase in renin release was observed. 7. Angiotensin II (AII) suppressed renin release in concentrations corresponding to plasma levels measured in the intact rat independently of its vasoconstrictor effects, whereas vasopressin in antidiuretic concentrations did not affect renin release. 8. AII, AI, synthetic tetradecapeptide renin substrate (TDP), crude and purified rat plasma renin substrate induced a dose-dependent reduction in renal plasma flow. SQ 20 881, a competitive inhibitor of converting enzyme, and low doses of 1-Sar-8-Ala-AII (saralasin), a competitive antagonist of AII, did not change renal plasma flow, whereas high concentrations of saralasin had a vasoconstrictor effect on their own. 9. Saralasin inhibited the vasoconstrictor effects of AII and TDP to a similar degree. SQ 20 881 inhibited the vasoconstrictor effects of AI and purified renin substrate, but did not influence the actions of TDP and the crude renin substrate preparation. 10. From these data it is concluded, that AI is converted into AII within the kidney at a rate of 1-2%. The vasoconstriction induced by the crude renin substrate probably does not involve the AII receptors. TDP may act by itself on the AII receptors or via the direct intrarenal formation of AII...