Angiotensin II stimulates angiotensinogen synthesis in hepatocytes by a pertussis toxin-sensitive mechanism

AbstractThe role of intracellular messengers in the stimulatory effect of angiotensin II on angiotensinogen synthesis and secretion in hepatocytes was examined. Angiotensinogen secretion was not influenced by modulators of intracellular calcium (calmidazolium, A 23187, Bay K 8644, methoxamine). In contrast, agents decreasing intracellular cAMP (angiotensin II, guanfacine) stimulated, and those increasing cAMP (isoproterenol, glucagon, forskolin) depressed angiotensinogen secretion. An inverse relationship was also observed between cAMP and angiotensinogen mRNA. Pretreatment of hepatocytes with pertussis toxin abolished the stimulation by angiotensin II. It is concluded that angiotensin II-induced stimulation of angiotensinogen synthesis is initiated by inhibition of adenylate cyclase

Flow versus pressure in the control of renin release in conscious dogs

In Goldblatt hypertension, renal artery stenosis reduces renal arterial pressure (RAP) and renal blood flow (RBF) and thereby increases plasma renin activity (PRA) levels. Although it is clear that reduction in RAP stimulates renin, the decrease in RBF may contribute to higher PRA as well. However, it has hitherto never been possible to dissociate a decrease in RBF from a concomitant decrease in RAP. To overcome this restriction, we used two protocols. 1) RAP was reduced in a single step to 70 +/- 0.2 mmHg (N = 8). RBF followed the sudden fall in RAP within 15 s but subsequently took on initial levels. In contrast, renal venous PRA increased from 0.95 +/- 0.22 to 5.6 +/- 1.4 ng angiotensin I.ml-1.h-1 (P &lt; 0.05) and remained at higher values even after RBF had regained control conditions. 2) Resonance between RAP and RBF was induced by superimposing slow sinusoidal RAP waves with a period length of 450 s (N = 9), leading to a phase shift of roughly 180 degrees (time delay, 241 +/- 12 s), i.e., RBF was maximal at minimal RAP. Under these conditions, renin release was only dependent on decrements in RAP (delay of only 27 +/- 8 s). In conclusion, RBF played no major role in renin release. </jats:p