Obese Zucker rats are normotensive on normal and increased sodium intake.

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.

Lateral parabrachial nucleus and angiotensin II-induced hypertension.

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 Sprague-Dawley 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 V1-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. During angiotensin II infusion, sham-lesion rats exhibited a progressive increase in arterial pressure and the depressor response to ganglion blockade and a decrease in urinary sodium excretion. No other variable was significantly changed. In rats with LPBN lesions, arterial pressure was significantly increased only on days 1 and 3 of angiotensin II infusion. No other variable was affected. It was concluded that ablation of the LPBN in rats prevented sustained hypertension during intravenous infusion of angiotensin II by interfering with neurogenic pressor mechanisms normally activated by the peptide.

Circulating angiotensin II and drinking behavior in rats.

This study was designed to investigate the effects on water drinking of acute and chronic increases in circulating angiotensin II (ANG II) concentrations in rats. Experiments were conducted in male Sprague-Dawley rats chronically instrumented with femoral arterial and venous catheters and permanently housed in metal metabolism cages. ANG II was infused intravenously either acutely (30 min-2 h) or chronically (3 days) in a dose range of 10-60 ng/min. In no instance did such infusions cause a statistically significant increase in water intake. Other experiments examined the influence of ANG II (10 ng/min iv) on drinking elicited by infusion of hypertonic sodium chloride (1.5 M at 3.5 microliters/min). ANG II administration did not increase drinking to a hypertonic saline stimulus or lower the osmotic threshold for drinking. Nitroprusside (12 micrograms/min) was infused for 30 min to produce hypotension and drinking. Water intake associated with this stimulus was not changed by blocking ANG II formation with enalapril (2 mg/kg iv) or by concomitant infusion of ANG II (10 ng/min iv). Finally, plasma ANG II concentrations were measured before and after 1-h intravenous infusion of saline or ANG II to determine the levels of circulating ANG II produced by the infusion rates used here. It is concluded that the range of circulating ANG II concentrations found under most physiological conditions in rats does not directly stimulate drinking or participate importantly in osmotic or hypotension-induced drinking.

Role of aldosterone in angiotensin II-induced hypertension in rats.

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.

Chronic hypertension produced by infusion of endothelin in rats.

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.

Effect of circulating vasopressin on arterial pressure regulation in rats.

It has been hypothesized that moderately increased blood levels of arginine vasopressin (AVP) contribute to the development and/or maintenance of hypertension. In this study, male Sprague-Dawley rats on a fixed 1 meq daily sodium intake received 10-day intravenous infusions of 0.2 and 2.0 ng.kg-1.min-1 AVP. The higher infusion rate was above the acute vasoconstrictor threshold for AVP administration and also produced a maximal antidiuretic effect. During chronic AVP administration, however, daily mean arterial pressure, heart rate, and body fluid composition were not changed, despite a maintained antidiuresis. To test the hypothesis that circulating AVP failed to cause hypertension as a result of sensitization of the baroreflex or a direct sympathoinhibitory effect of the peptide, additional experiments were performed in rats subjected to sinoaortic denervation (SAD) or ablation of the area postrema (APX). Infusion of AVP for 10 days into SAD or APX rats caused a sustained antidiuresis but did not change arterial pressure, heart rate, or body fluid composition. In all groups of rats, the depressor response to ganglionic blockade (20 mg/kg hexamethonium) was used to estimate the autonomic component of resting arterial pressure; no change in autonomic cardiovascular control was found using this method in any of the groups during AVP infusion. Long-term elevation of plasma AVP in rats, therefore, does not cause hypertension or significantly affect autonomic regulation of arterial pressure.

The area postrema in deoxycorticosterone-salt hypertension in rats.

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.