Endothelin, a potent vasoconstrictor peptide synthesized by the vascular smooth muscle endothelium, was chronically infused into male Sprague-Dawley rats to determine whether a long-term increase in circulating endothelin levels would cause a sustained elevation in mean arterial pressure. Rats were catheterized, housed in metabolic cages, and maintained on a fixed 6 meq/day sodium intake throughout the experiment with daily measurements including mean arterial pressure, heart rate, water intake, urine output, urinary sodium excretion, urinary potassium excretion, cardiac output, total peripheral resistance, and stroke volume. Infusion of endothelin-1 (ET-1) at rates of 3, 5, or 7.5 pmol/kg/min for 7 days was associated with significant, sustained, and dose-dependent increases in mean arterial pressure and smaller less consistent elevations in total peripheral resistance. Other parameters were unaffected. Similar results were observed in rats receiving endothelin-3 (ET-3), except that a higher dose of ET-3 was required. These results indicate that elevated blood levels of endothelin could produce a maintained hypertension without sodium or water retention and that the hemodynamic basis for the increased mean arterial pressure is similar to that seen in most other forms of experimental and clinical hypertension. monary baroreceptor reflexes, renal fluid loss, or any of these mechanisms together. If either circulating or locally released endothelins serve a vasoconstrictor function in hypertension, then they should be capable of producing a long-term pressor action not effectively countered by the mechanisms listed above.It was the purpose of this study, therefore, to investigate the hemodynamic responses to endothelin administered as an infusion over a period of 7 days to allow observation of the effects of activation of homeostatic pressure regulatory mechanisms. Also, previous investigations 12 - 13 have shown that differences might exist in the biological activity or metabolic fate of ET-1 and ET-3, which differ in six amino acid residues. Thus, an additional purpose of this study was to compare the hemodynamic responses to these two homologous peptides. MethodsMale Sprague-Dawley rats (340-380 g) were anesthetized with halothane (1.0 vol% in O 2 at 1.0 1/min). A midline thoracotomy was performed for implantation of an aortic directional pulsed Doppler flow probe. Probe leads were directed into a subcutaneous pocket in the animal's back, and the rats were allowed 5 days of recovery. After this recovery period, rats were anesthetized with pentobarbital sodium (50.0 mg/kg i.v.). Polyvinyl silicone catheters were surgically implanted into the abdominal aorta and a femoral vein through the left femoral vessels

The objective of this study was to determine if ablation of the lateral parabrachial nucleus (LPBN) would prevent angiotensin II-induced hypertension in rats. Thirteen male SpragueDawley rats were studied. Bilateral electrolytic lesions in the LPBN were produced in six rats; the remaining seven rats were subjected to sham lesion surgery only. All rats were instrumented with vascular catheters and housed in metabolism cages. Daily measurements during the 16-day protocol included arterial pressure, heart rate, water intake, urine output, and urinary sodium excretion. Periodically throughout the protocol depressor responses to ganglion blockade and to blockade of V,-type vasopressin receptors also were measured. The protocol was divided into three control-period days, 10 days of continuous (24 hr/day) angiotensin II infusion (10 ng/min i.v.), and three recovery-period days. There were no significant differences between the two groups of rats for any variable during the control period.

The purpose of this study was to determine whether genetically obese Zucker rats have higher arterial pressures than lean littermates on normal and high sodium intakes. Mean arterial pressure was directly measured in chronically instrumented Zucker rats (six lean [weight, 345.8 +/- 8.0 g] and five obese [529.0 +/- 6.2 g]) for 2 weeks on both a normal (2 meq sodium/day) and high (6 meq sodium/day) sodium intake (7 days each). In addition, daily heart rate, water intake, urine output, urinary sodium excretion, urinary potassium excretion, and weekly fasting plasma insulin levels were measured. Obese rats exhibited significantly lower heart rate and greater water intake and urine output compared with lean rats whether maintained on control or high sodium intakes. Urinary sodium excretion, however, was identical in lean and obese rats throughout the experiment. Fasting plasma insulin levels in obese rats were seven times greater than those in lean rats. When the rats were maintained on a 2 meq/day sodium intake, mean arterial pressures obtained from the two groups were similar: 103 +/- 1 versus 106 +/- 1 mm Hg (lean versus obese). An increase in sodium intake did not significantly affect mean arterial pressure in either group: 101 +/- 1 versus 105 +/- 1 mm Hg (lean versus obese). These results indicate that at 12-14 weeks of age, male obese Zucker rats do not exhibit higher resting arterial pressures than lean littermates when maintained on normal or high sodium intake.

SUMMARY Ablation of the area postrema in rats prevents sustained hypertension during angiotensin II infusion and after unilateral renal artery constriction (two-kidney, one clip hypertension). The current experiment was performed to determine whether an intact area postrema is required for hypertension development in a low renin model of experimental hypertension in rats. In 11 rats, the area postrema was destroyed using electrical current; the extent and specificity of each lesion was confirmed later by blind histological analysis. In 12 rats, sham operations were performed. All rats were uninephrectomized and drank saline. During once-weekly injections of deoxycorticosterone pivalate (5 mg/wk) for 4 weeks, sham-operated rats (n = 10) showed a significant increase in mean arterial pressure (Days 6-28) and saline intake (Days 12-28), but no significant increase in sodium or water retention. Deoxycorticosterone-treated rats with area postrema ablation (n = 9) exhibited no change in arterial pressure, sodium retention, or water retention, but a significant increase in saline intake (Days 17-28). Plasma renin activity was equally suppressed in both groups of rats. The depressor response to ganglion blockade with hexamethonium (20 mg/kg i.v.) was significantly increased during the 2nd, 3rd, and 4th weeks of steroid treatment in sham-operated, but not area postrema-ablated, rats. Four rats (2 sham-operated; 2 ablated) showed no change in any variable over 28 days in the absence of steroid treatment. It is concluded that the area postrema may be important in some non-angiotensin-dependent forms of experimental hypertension, possibly by affecting neurogenic control mechanisms. (Hypertension 9 [Suppl III]: III-206-III-209, 1987) KEY WORDS • area postrema • mineralocorticoid hypertension • arterial pressure • rat T HE area postrema (AP) is a small, highly vascular structure at the caudal end of the fourth cerebral ventricle on the dorsal medulla. The permeability of this brain structure to blood-borne substances and its substantial connectivity to other brain regions known to be important in neural cardiovascular regulation 1 make it a likely site for integration of hormonal and neural signals involved in maintaining cardiovascular homeostasis. Detailed studies by Barnes and colleagues 2 have established that the AP in the dog can be activated by acute increases in circulating angiotensin II (ANG II) so as to cause a sympathetically mediated increase in arterial pressure. In the rat, on the other hand, it was reported that the AP did not partici-

Initial experiments demonstrated that a 1-h infusion of 10 ng/min angiotensin II (ANG II) into rats causes an increase in plasma aldosterone concentration (PAC) and that chronic administration of aldosterone alone to rats on increased sodium intake causes hypertension. We therefore hypothesized that a portion of the hypertensive effect of chronic ANG II infusion is accompanied by and dependent on chronic release of aldosterone. To test this hypothesis, 10 ng/min ANG II or saline was infused into chronically instrumented rats housed in metabolism cages. Fifteen rats were maintained on a high sodium intake (6 meq/day); 10 received ANG II and 5 received saline. Ten other rats were maintained on a normal sodium intake (2 meq/day); five received ANG II and five received saline. PAC was measured using a commercial radio-immunoassay kit. Mean arterial pressure (MAP), heart rate, water intake, urine output, and urine electrolytes were measured daily during 3-day control, 16- or 28-day infusion, and 4-day recovery periods. Compared with saline-infused rats, ANG II-infused rats on high sodium intake had normal values for all variables except MAP, which was significantly elevated during ANG II infusion. In the normal sodium group, none of the variables were consistently different during ANG II infusion compared with control. These results suggest that ANG II-induced hypertension in the rat is sodium dependent, that plasma aldosterone does not play a major role in ANG II-induced hypertension in the rat, and that a small chronic increase in circulating ANG II does not necessarily lead to a detectable sustained increase in PAC.