SUMMARYThe effect of surgical ablation of the area postrema on acute (5-10 minutes) and chronic (5-10 days) increases in mean arterial pressure produced by intravenous infusion of angiotensin II hi conscious, instrumented rats was studied. In agreement with previous studies, pressor responses of area postrema-ablated rats (a = 11) to acute angiotensin II infusion were identical to those of control sham-lesioned rats (n = 13). In these same rats, however, a 5-day infusion of angiotensin II produced a sustained hypertension hi the sham-lesioned group whereas mean arterial pressure was increased only transiently (1-3 days) hi the area postrema-ablated rats. No differences before infusion of arterial pressure, heart rate, water intake, urinary sodium excretion, and urinary potassium excretion were observed between sham-lesioned and area postrema-ablated rats; only arterial pressure was changed significantly during angiotensin II infusion hi either group. Twenty-four hours after terminating angiotensin II infusion, mean arterial pressure was within the normotensive range hi both shamlesioned and area postrema-ablated rats. In a separate group of sham-lesioned (n = 13) and area postrema-ablated (n = 12) rats, angiotensin n was infused intravenously for a 10-day period; mean arterial pressure was increased significantly over the entire 10-day infusion hi sham-lesioned rats, but for only 1 day hi area postrema-ablated rats. An intact area postrema appears necessary for the development of chronic, but not acute, hypertension during intravenous infusion of angiotensin II hi the rat. Supported by National Heart, Lung, and Blood Institute Grants HL24111 andHL32981.Address for reprints: Dr. Gregory D. Fink, Dept. of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824.Received January 27, 1986; accepted October 20, 1986. perimental hypertension. A detailed analysis 1 of many of these studies led to the conclusion that ANG II does not cause chronic hypertension by direct vascular constriction, but rather by an ability to stimulate a more slowly developing (hours to days) pressor mechanism: a mechanism whose sensitivity to ANG II increases with prolonged exposure to the hormone. Actions of ANG II on aldosterone secretion, 2 renal handling of salt and water,

Intracranial injection of angiotensin II (AII) at three brain sites elicited near simultaneous dipsogenic and pressor effects in rats. Both effects were maximal, occurred with the shortest latencies, and at the lowest doses of AII when the cannula terminated precisely within the parenchyma of the subfornical organ (SFO). Pressor effects were produced by SFO injection of a dose of AII (0.1 pg) which approximates plasma AII concentrations at the high end of the physiological range. Both the drinking and pressor effects were blocked by saralasin. Injections of AII at sites immediately adjacent to SFO produced smaller effects with longer latencies. These results ruled out the possibility that SFO injections were effective via leakage to alternative sites. The pressor effect of AII at the SFO remained in animals under chloralose anesthesia, demonstrating that it is not an artifact of drinking behavior. These results indicate that the SFO is a site of AII pressor action, and confirm previous demonstrations that the structure is a site of AII drinking action.

The effects of ablation of the nucleus medianus on drinking and vasopressin secretion were studied in male Long-Evans rats. The amount of water drunk in 1 h was assessed after subcutaneous injection of 5.8% NaCl (13.34 mosm/kg) or of angiotensin II (1.5 mg/kg). In a separate test with no water available, plasma vasopressin was measured 15 min after the above dose hypertonic saline. Ablation of the nucleus medianus, or the dorsal and anterior portions of the nucleus medianus, blocked drinking to hypertonic saline or angiotensin II and attenuated the vasopressin response to hyperosmolality. Animals with septal or diagonal band lesions showed responses comparable to sham-operated rats. These results indicate that a neural pathway important for fluid balance passes through, or terminates in, the nucleus medianus.

The pressor effect of intravenous angiotensin II (AII) was compared in the unrestrained rat before and after electrolytic lesions of the subfornical organ (SFO), the circumventricular organ of the dorsal third cerebral ventricle. Abdominal aortic and venal caval catheters were used to measure arterial pressure and to infuse solutions, respectively. The pressor effect of AII was significantly reduced following complete SFO lesions but was unaffected by partial SFO lesions or by control lesions in adjacent tissue. The pressor effect of intravenous infusion of the alpha-adrenergic agonist, phenylephrine, was unaffected by any of these lesions. In agreement with experiments demonstrating that SFO injection of AII increases arterial pressure, the present results suggest that a significant portion of the pressor action of circulating AII is centrally mediated, and that the SFO participates in this mediation.

No abstract

No abstract

A chymase (also referred to as angiotensin I-convertase) specific for the conversion of angiotensin (Ang) I to Ang II has been identified in human heart. This serine protease is also present in dog and marmoset vasculature. We examined the vasoconstrictor effects of Ang II putatively generated from an angiotensin-converting enzyme (ACE)-resistant convertase synthetic substrate (SUB) in vivo and in vitro. In marmosets, SUB (7 to 700 /ig/kg IV) or Ang I (0.1 to 30 /ig/kg) caused similar dose-dependent increases in mean arterial pressure (10 to 100 mm Hg) and decreases in heart rate. Pressor effects of SUB were slightly attenuated at low (but not high) doses by captopril (CAP, 1 mg/kg IV) and blocked by losartan (5 mg/kg IV); in contrast Ang I pressor effects were substantially blocked by both. In isolated canine superior mesenteric artery, Ang I-induced contraction was

Previous studies have shown that electrical stimulation of the rat anteroventral third ventricle (AV3V) region produces a characteristic pattern of hemodynamic effects, i.e., renal and mesenteric vasoconstriction, and hindquarters vasodilation. In the present study, we localized the vasoconstrictor and vasodilator effects to specific subregions of the AV3V. In urethan-anesthetized rats prepared with arterial catheters and pulsed Doppler flow probes, we assessed the effects of electrical stimulation of four nuclei within AV3V on mean arterial pressure and renal, mesenteric, and hindquarters resistance. These nuclei were the organum vasculosum lamina terminalis (OVLT), ventral nucleus medianus (median preoptic nucleus), anterior (precommissural) nucleus medianus (median preoptic nucleus), and periventricular preoptic nuclei. Stimulation was carried out by use of a tungsten microelectrode. Stimulation of the OVLT consistently provoked stimulus-locked increases in arterial pressure coupled with increases in mesenteric and renal vascular resistance. Ganglionic blockade with chlorisondamine prevented these responses, demonstrating that they were mediated neurogenically. Stimulation of the three remaining nuclei produced decreases in arterial pressure, hindquarters vasodilation, and little change in mesenteric and renal vascular resistance. No changes in heart rate were observed with stimulation of any of the four nuclei. These results suggest that the vasoconstrictor and pressor functions of the AV3V region are localized in or near the OVLT region, whereas the remaining nuclei of the AV3V region mediate vasodilator and depressor responses.