Pressor and intra-renal effects of angiotensins I and II, and noradrenaline, in anaesthetized and conscious sheep. The effects of halothane anaesthesia on pressor sensitivity and electrolyte shifts: the proposed use of angiotensin I in treating septicaemia and septic shock.

The pressor and intra-renal actions and effects of octa - and deca-peptides angiotensins II and I and of the catecholamine noradrenaline, in anaesthetized and conscious sheep, are considered. The halothane anaesthetic substantially lowers pressor sensitivity to both peptides but does not influence their ability to liberate K(+) ions into the circulating plasma. In comparison with angiotensin II, both angiotensin I and noradrenaline -- with direct presentation to the kidney -- are ineffective in decreasing intra-renal blood flow. However, with left ventricular injection, both pressor compounds immediately increase the blood pressure, as does angiotensin II. Combined doses of the decapeptide and catecholamine are thus highly effective in raising the blood pressure while having a minimal effect on blood flow through the kidney. This overall situation could provide a basis for treating clinical shock, especially regarding septicaemia and septic shock. The lowered hind-limb blood flow, with administration of the pressor compounds into the femoral artery, contrasts strongly with the raised flow resulting from intravenous injection. Experimental procedures to establish, or otherwise, relevant hypothetical situations are detailed.

Hind-limb/hind-quarter vascular resistance and blood flow changes: possible intrinsic renin--angiotensin system involvement.

For many years there was a general belief that the enzyme renin, having been secreted into the circulation by the kidney in response to appropriate stimuli, initially generates the inactive decapeptide angiotensin I in the bloodstream. This is then converted to the biologically active octapeptide angiotensin II by angiotensin converting enzyme on or near, vascular surface receptors both in the lungs and in the organs supplied by the systemic circulation. The results of various investigations have, however, latterly led to the conclusion that the overall system is widely distributed throughout the vasculature with the local intracellular formation of angiotensin II. In this review the reckoned intrinsic renin-angiotensin activity in hind-limb/hind-quarter is discussed with particular regard to the widespread use of radioimmunoassay, together with a consideration of other factors, more especially ACE inhibition, affecting the relevant regional vascular resistance and blood flow.

A peptide family being re-united: the angiotensins coming in from the cold.

The renin-angiotensin-aldosterone system is now considered to be far more complex than previously thought when the vasoconstrictor and other physiological effects of the octapeptide angiotensin II in the circulating blood were emphasized. The reasons for this altered viewpoint, involving angiotensins other than the octapeptide in the regulation of blood pressure, water and electrolyte homeostasis, are briefly advanced and discussed.

Receptors for angiotensins I and II: their relevance to renal haemodynamics, blood pressure control and hind-limb blood flow.

The well established differential pulmonary handling of angiotensins I and II indicates the possibility that vascular receptors for the deca- and octa-peptides do not necessarily involve common sites in the renal vasculature either. Experimental findings involving haemodynamic changes within the kidney in anaesthetised and conscious sheep, with utilization of the angiotensins, and also of noradrenaline, are briefly presented; the implications of the intra-renal water and creatinine transfers are discussed, especially as they concern the possible location of angiotensin receptors in the renal blood vessels. Other aspects of the relationships between the peptides are also taken into account particularly with regard to a postulated angiotensin I [NaCl] dependent peritubular capillary antidiuretic action, angiotensin converting enzyme inhibition, Goldblatt clamp induced hypertension and blood flow through the hind-limbs.

Twenty years of investigating angiotensin activity: an overview.

A short account of the renin-angiotensin-aldosterone system is given with emphasis on the relationship between the octapeptide angiotensin II and its decapeptide precursor angiotensin I. Although the decapeptide is generally assumed to have no biological activity, extensive investigations have indicated that such an assumption is almost certainly unjustified. The implications of the findings are briefly outlined and discussed.

The question of lung involvement in angiotensin II-induced rises in circulating plasma (K+) and arterial blood pH.

The reported patterns of raised plasma [K+] and arterial blood pH associated with intravenous infusion of angiotensin II in experimental animals are discussed with emphasis on the possible role of the lungs in these observed responses.

Do angiotensin-induced changes in sheep renal venous blood and plasma composition indicate a reversal of glomerular filtration?

Angiotensin II markedly lowers the relative cell content of renal venous blood both with injection into the jugular vein and into the left ventricle of anaesthetised sheep; angiotensin I has a similar effect in this regard when given intravenously but the decreased cellular fraction is much less evident with left ventricular injection when the direct presentation to the kidneys precludes prior intra-pulmonary conversion to angiotensin II. The angiotensins also produce readily demonstrable alterations in renal venous plasma electrolyte, protein, creatinine and urea levels. This pattern of changes is related to associated intra-renal haemodynamics, reverse filtration of proximal tubular fluid, a possible anti-diuretic action of angiotensin I itself on the peritubular capillaries and acute renal failure in man and experimental animals.

Influence of angiotensin II on the concentration of arterial plasma electrolytes in anaesthetized sheep.

Angiotensin II and I significantly raised potassium and lowered sodium and chloride ion concentrations in arterial plasma, with peak changes occurring in the first 2 min of a 6-min infusion period. The octapeptide increased the arterial K+ level in a dose-dependent manner, but the response showed tachyphylaxis when multiple infusions of 6-min duration were administered after a recovery interval of only 5 min. Raising the arterial blood pressure by 20-33 mmHg with adrenaline and noradrenaline failed to account for the increase in arterial plasma K+ concentration produced by the two peptides. These findings, in particular the rise in K+ concentration, are discussed in relation to possible mechanisms by which angiotensin II affects arteriolar tone.

Radioimmunoassay of unprocessed sheep blood extracts to follow angiotensin metabolism.

The acceptability of radioimmunoassay to determine the levels of compounds antigenic to anti-angiotensin antibodies, in unprocessed methanolic blood extracts, was established for sheep blood. This approach was used to follow the clearance of antigenic compounds after administration of angiotensins I and II and fragments of angiotensin II in anesthetized sheep. The organs supplied by the systemic circulation and also the lungs effectively removed angiotensin I, but the removal of octapeptide occurred only in the peripheral tissues. The blood concentrations of compounds reacting with the anti-angiotensin II antibody always increased with passage of angiotensin I through the pulmonary circulation but not with passage of angiotensin II. The results indicate that factors other than efficiency of removal by the tissue is important in establishing blood levels. The sites of administration and of sampling were shown to be important in relation to ratios of the concentrations of antigenic material. There was a similar uptake of both hormones in the kidney; the relative inability of angiotensin I to reduce renal blood flow, therefore, does not result from a failure of uptake.