No abstract

H-Prazosin and^H-rauwolscine binding sites were identified in a membrane suspension prepared from albino rabbit iris + ciliary body. Scatchard analysis of saturation binding experiments demonstrated that both %-prazosin and %-rauwolscine bind to a single population of binding sites with Krj values of 0.87 nM and 5.33 nM, respectively. Bmax values of 65.7 and 198 fmol/mg protein were obtained for^H -prazosin and 3jj-rauwolscine, respectively. Displacement studies by several adrenergic agonists and antagonists indicated that^H -prazosin and^H-rauwolscine labelled a^-and o^-adrenoceptors, respectively, in the iris + ciliary body. Epinephrine, norepinephrine and phenylephrine were able to stimulate the synthesis of 3H-inosit.0l. phosphates in ciliary processes labelled with 3H-inositol, with EC50 values of 2.4, 12 and 10 yM, respectively. The corresponding maximum stimulations of basal activity were 433, 430 and 283%, respectively. Phenylephrine behaved like a partial agonist in this assay. The norepinephrine response could be potently antagonized by prazosin (K^= 27 nM), with rauwolscine being 285-fold less potent. An epithelial cell suspension was prepared from the ciliary process. Stimulation of phosphatidylinositol turnover by norepinephrine (0.1 mM) was observed, and this could be blocked by prazosin (10 \M), thus, indicating the presence of oci-adrenoceptors, coupled to phosphatidylinositol turnover, in epithelial cells of the rabbit ciliary process.

In the guinea-pig, perindopril inhibited plasma angiotensin converting enzyme (ACE) by 90% when given orally at 2 mg/kg/day during 10 days. Mean blood pressure and plasma aldosterone, cortisol and vasopressin concentrations were not modified by this treatment, while plasma renin activity (PRA) and plasma angiotensin I concentrations increased significantly. The same parameters were studied using a constant intravenous 30 min-infusion of atrial natriuretic peptide (ANP) (0.1 micrograms.kg-1min-1). This dose of ANP infused to anesthetized guinea-pigs induced a significant decrease in mean blood pressure (about -20%) in control and in perindopril treated animals. In ANP infused animals, plasma aldosterone and cortisol concentrations decreased similarly in both groups by about -50%, whereas plasma vasopressin concentrations increased in controls (+169%) but not in perindopril treated guinea-pigs. An increase in PRA and plasma angiotensin I concentrations was observed in both groups after the infusion of ANP. Thus, when ANP demonstrated an potent hypotensive effect a concomitant increase in PRA occurred. The rise observed in vasopressin concentration in control animals was probably mediated by angiotensin II. The fall in plasma aldosterone and cortisol concentrations observed after ANP infusion demonstrated a direct potent action of ANP at the adrenal levels.

The effects of dopamine on plasma renin-angiotensin-aldosterone system vasopressin levels and blood pressure were studied in anesthetized guinea-pig. The inhibition of the angiotensin converting enzyme with perindopril permitted assessment of the role of the renin-angiotensin system. In perindopril-treated guinea-pigs, the activity of angiotensin-converting enzyme was decreased by 90% with simultaneous increases in plasma renin activity and angiotensin I concentration; aldosterone and vasopressin levels, blood pressure and heart rate were not modified. Dopamine depressed mean arterial pressure by 30% and increased heart rate (8%) in controls. Dopamine infusion did not affect either plasma renin activity or angiotensin I concentration or angiotensin-converting enzyme activity in control animals. But in perindopril pretreated animals it further increased plasma renin activity (88%) and angiotensin I concentration (35%). Finally, in controls, dopamine infusion increased plasma vasopressin concentrations (91%) whereas this increase did not occur in perindopril treated animals.