The effect of altered sodium balance upon renal vascular reactivity to angiotensin II and norepinephrine in the dog. Mechanism of variation in angiotensin responses.

Abstract

A B S T R A C T The mechanism whereby the vasoconstrictor response to angiotensin II (A,,) is influenced by sodium balance or disease is unclear. To explore this question, the renal vascular responses (RVR) to intrarenal injections of subpressor doses of A,, and norepinephrine were studied in dogs with an electromagnetic flowmeter. Acute and chronic sodium depletion increased plasma renin activity (PRA) and blunted the RVR to A,,, while acute sodium repletion and chronic sodium excess plus desoxycorticosterone acetate decreased PRA and enhanced the RVR to All.The magnitude of the RVR to Al1 was inversely related to PRA. The RVR to norepinephrine was unaffected by sodium balance and was not related to PRA. Inhibition of the conversion of angiotensin I to Al, by SQ 20,881 during sodium depletion lowered mean arterial blood pressure (MABP), increased renal blood flow (RBF), and enhanced the RVR to Al, but not to norepinephrine. Administration of bradykinin to chronically sodium-depleted dogs also lowered the MABP and increased RBF but had no effect on the RVR to A11. SQ 20,881 had no effect on MABP, RBF, or the RVR to Al1 in the dogs with chronic sodiuni excess and desoxycorticosterone acetate. Administration of indomethacin to chronically sodium-depleted dogs lowered RBF but did not influence the RVR to A,,.The results indicate that the RVR to A,, is selectively influenced by sodium balance and that the magnitude of the response is inversely related to the availability of endogenous AII The data did not suggest that the variations in the RVR to A,, were because of direct effects of sodium on vascular contraction, changes in

Participation of the Prostaglandins in the Control of Renal Blood Flow during Acute Reduction of Cardiac Output in the Dog

“…The absence ofrenal vasoconstriction during the acute reduction of cardiac output is noteworthy because arterial plasma renin activity and arterial plasma concentration of norepinephrine were markedly elevated in response to thoracic caval obstruction (Tables III and IV) and because angiotensin II and norepinephrine are both renal vasoconstrictors (15). During acute heart failure, the renal venous renin activity and renal venous plasma norepinephrine concentration increased above control values.…”

“…Renal prostaglandin synthesis is increased in sodium depletion (30), hemorrhagic hypotension (31), renal artery constriction (31), and cirrhosis with ascitis (33). In all these conditions, administration of inhibitors of prostaglandin synthesis reduces renal blood flow (12,15,16,31). The mechanism(s) whereby the prostaglandins attenuate renal vasoconstrictor mechanisms remains to be determined.…”

“…In particular, prostaglandins are known to be involved in renal blood flow control in a variety of conditions in which the renin-angiotensin system is activated. Although inhibition of the synthesis of prostaglandins has little or no effect upon renal blood flow during control conditions (10)(11)(12), it elicits or augments the reductions of renal blood flow that occur during hemorrhagic hypotension (13,14), sodium depletion (15), and in patients with cirrhosis and ascitis (16).…”

Dietary and pharmacological alterations in endogenous angiotensin II: effect on noradrenaline pressor responsiveness in the rat

“…Lowering endogenous All levels with acute volume repletion (Oliver & Cannon, 1978) also enhanced the pressor response to All in rats with a low sodium intake. These results are consistent with the postulate that elevations in endogenous angiotensin II levels result in an attenuated response to this peptide as has been reported previously (Thurston & Laragh, 1975;Oliver & Cannon, 1978;Smyth & Fung, 1984). These results substantiated the sensitivity of our system for detecting differences in pressor responsiveness.…”

“…Previous studies have demonstrated that changes in angiotensin II receptor occupancy, following alterations in endogenous angiotensin II concentrations, were responsible for changes in response to this peptide (Thurston & Laragh, 1975;Oliver & Cannon, 1978). Thus, reduction of endogenous angiotensin II levels either by increased sodium intake (Reid & Laragh, 1965;Slack & Ledingham, 1976), converting enzyme inhibition (Thurston & Laragh, 1975), bilateral nephrectomy (Swales et al, 1975) or prostaglandin synthetase inhibition (Smyth & Fung, 1984) would be expected to enhance the pressor responsiveness to exogenously administered angiotensin.…”