It is generally presumed that plasma levels of angiotensin II immunoreactivity primarily reflect the contribution of kidney renin. Studies involving serial measurements of plasma renin activity, plasma and cerebrospinal fluid angiotensinogen, and immunoreactive angiotensin I and angiotensin II within 48 hours after bilateral nephrectomy do not support this view. In 15 conscious, instrumented dogs, samples of arterial blood and cerebrospinal fluid were obtained before and between 1 and 48 hours after bilateral nephrectomy. During the first 12 hours after bilateral nephrectomy, there was a rapid fall of both plasma renin activity (nondetectable levels) and angiotensin I immunoreactivity (from 171 ± 22 pg/ml to 39 ± 13 pg/ml) whereas plasma and cerebrospinal fluid angiotensin n immunoreactivity remained unchanged (from 22 ± 5 to 22 ± 7 pg/ml), and from 5 ± 2 to 7 ± 3 pg/ml, respectively). These effects of bilateral nephrectomy were still evident at 48 hours and were accompanied by significant (p < 0.01) increases in both plasma and cerebrospinal fluid angiotensinogen. Plasma extracts from bilaterally nephrectomized dogs were injected into anesthetized rats to examine their bioactivity. The extracts produced pressor responses that were completely blocked by infusion of the angiotensin II receptor antagonist [Sar1.Ile8] angiotensin II. To ascertain whether or not the angiotensin II immunoreactivity detected in plasma of bilaterally nephrectomized dogs was the authentic octapeptide, blood was also obtained 48 hours after bilateral nephrectomy. Peptides were extracted from plasma on Sep-Paks and analyzed by high pressure liquid chromatography. The plasma extract from bilaterally nephrectomized dogs migrated with the same retention time as Ile5-angiotensin II. These data provide new evidence for the possibility that nonrenal factors account for the presence of basal levels of plasma and cerebrospinal fluid angiotensin II immunoreactivity in conscious dogs 48 hours after bilateral nephrectomy.

To elucidate whether the presence of angiotensin II immunoreactivity (ANG II-ir) in the cerebrospinal fluid (CSF) of the dog is in part due to passage of the peptide across the CSF-blood-brain barrier, [Ile5] angiotensin II (ANG II) was infused intravenously for 7 days in conscious, trained dogs at a rate of 10 micrograms/kg/day. Mean arterial pressure (MAP) and heart rate were monitored each day, and samples of arterial blood and CSF (with a catheter secured into the cisterna magna) were drawn at regular intervals for determination of catecholamine levels, ANG II-ir, and electrolyte levels. Within 2 days after ANG II infusion, MAP stabilized at 35 +/- 1 mm Hg (mean +/- SE, p less than 0.001) above control values. The hypertension was associated with bradycardia, suppressed plasma renin activity, and a fall in both plasma and CSF Na+ concentrations. These changes coincided with a considerable and sustained decrease in the levels of plasma and CSF norepinephrine. On the other hand, levels of epinephrine and K+ in the two compartments remained unchanged. Although concentration of ANG II-ir in plasma was augmented markedly (368% above control values, p less than 0.001), ANG II-ir in the CSF remained within the low values measured in the control period.(ABSTRACT TRUNCATED AT 250 WORDS)

We have investigated the relative importance of angiotensin and vasopressin in the regulation of arterial pressure following permanent interruption of supraspinal sympathetic influences. To accomplish this aim, the spinal cord of 12 dogs was transected just above the intervertebral foramen of C-6; several days later, we gave first a potent blocker of the vasculotropic actions of vasopressin and 40 min later captopril. The same experiment was performed in other dogs with the drug order reversed. Mean arterial pressure and heart rate were recorded continuously and blood samples were taken to measure plasma renin activity and plasma catecholamines. All studies were carried out at three levels of hydration: normal, after 36 h water deprivation and following an overnight infusion of 0.9% saline. Conscious dogs with complete surgical sympathectomy by spinal cord section had normal mean arterial pressure, heart rate and plasma renin activity but undetectable levels of catecholamines. Captopril produced significant falls in mean arterial pressure that were greatest in water deprivation and least in volume loading, whether the drug was given before or after treatment with the vasopressin antagonist. On the other hand, the vasopressin antagonist modified mean arterial pressure only in the water deprived state. In spinal dogs the renin angiotensin system assumes a primary role in maintaining normal mean arterial pressure at various extremes of body fluid volumes. Vasopressin plays a role only after removal of the two dominant systems.