Vascular responsiveness in rats resistant to aldosterone-salt hypertension.

Wistar-Furth rats have been shown to be resistant to mineralocorticoid-salt hypertension, but the mechanism for this resistance is unknown. In the current experiments, adult male Wistar and Wistar-Furth rats were given a subcutaneous aldosterone infusion (0.15 microgram/hr) for 4 weeks, and changes in blood pressure and vascular reactivity were studied. Rats received a 1% NaCl, 0.2% KCl solution to drink. After 4 weeks of aldosterone infusion, systolic blood pressure measured using a tail-cuff technique had increased by 60 mm Hg in Wistar rats but was unchanged in Wistar-Furth rats. Hypokalemia occurred in both strains in response to the aldosterone infusion. Isolated, helically cut strips of common carotid artery and aorta were prepared for isometric force recording. Cumulative concentration-response curves to norepinephrine, serotonin, KCl, calcium, nitroprusside, and acetylcholine were performed in carotid artery strips, and concentration-response curves to ouabain were performed in aortic strips. Increased vascular contractile sensitivity to KCl, ouabain, norepinephrine, and serotonin was observed in vessels from Wistar rats treated with aldosterone and salt. The same treatment in Wistar-Furth rats produced only increased vascular sensitivity to ouabain and serotonin, and these changes were of smaller magnitude than those seen in Wistar rats. Aldosterone-salt treatment produced decreased vascular sensitivity to acetylcholine and nitroprusside in both Wistar and Wistar-Furth rats. These results support the hypothesis that resistance of Wistar-Furth rats to aldosterone-salt hypertension is due to resistance to the effects of aldosterone-salt treatment that normally result in increased vasoconstrictor sensitivity.

Adrenal-dependent change in vascular reactivity in stroke-prone spontaneously hypertensive rats.

Tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP) exhibit oscillatory contractions in response to norepinephrine. This type of oscillatory behavior does not occur in tail arteries from normotensive Wistar-Kyoto rats (WKY). We have shown that the traits of norepinephrine-induced oscillatory activity and high blood pressure are genetically associated in SHRSP, suggesting that oscillatory activity is a primary vascular abnormality that contributes to hypertension in this strain. In the present experiments, two approaches were used to test the hypothesis that adrenal mineralocorticoids modulate expression of this genetically determined vascular abnormality in SHRSP. First, the effect of adrenalectomy on blood pressure and oscillatory activity was determined in SHRSP that underwent bilateral adrenalectomy 3 weeks before experimentation. Second, the effect of deoxycorticosterone acetate (DOCA)-salt treatment on blood pressure and oscillatory activity was determined in 1) rats with no genetic background for oscillatory activity (WKY) and 2) progeny of SHRSP x WKY (F1 rats). Helically cut tail artery strips from all rats were mounted in isolated tissue baths for isometric force recording. Vessels were exposed to norepinephrine (6 x 10(-10) to 6 x 10(-6) M) for 20 minutes at each concentration. Oscillatory activity was defined as the sum of the phasic contractile amplitudes for all oscillations occurring during the final 10 minutes of norepinephrine incubation. Adrenalectomy markedly decreased blood pressure and oscillatory activity in SHRSP.(ABSTRACT TRUNCATED AT 250 WORDS)

Area postrema is critical for angiotensin-induced hypertension in rats.

The 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 in conscious, instrumented rats was studied. In agreement with previous studies, pressor responses of area postrema-ablated rats (n = 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 in the sham-lesioned group whereas mean arterial pressure was increased only transiently (1-3 days) in 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 in either group. Twenty-four hours after terminating angiotensin II infusion, mean arterial pressure was within the normotensive range in both sham-lesioned and area postrema-ablated rats. In a separate group of sham-lesioned (n = 13) and area postrema-ablated (n = 12) rats, angiotensin II was infused intravenously for a 10-day period; mean arterial pressure was increased significantly over the entire 10-day infusion in sham-lesioned rats, but for only 1 day in 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 in the rat.

Area postrema ablation and vascular reactivity in deoxycorticosterone-salt-treated rats.

In rats, central administration of the neurotoxin 6-hydroxydopamine prevents hypertension and certain functional vascular changes after deoxycorticosterone (DOC)-salt treatment. In this study, the effect of electrolytic ablation of the area postrema on blood pressure and vascular reactivity in DOC-salt-treated rats was examined. Four treatment groups of rats were studied (n = 5 in each): area postrema lesion, DOC-salt (DOC pivalate, 5 mg/wk s.c. for 5 weeks); sham lesion, DOC-salt; area postrema lesion, control; and sham lesion, control. Helically cut strips of carotid artery, aorta, and mesenteric artery were prepared for isometric force recording. Area postrema lesion attenuated hypertension in DOC-salt rats (mean arterial pressure, 107 vs 123 mm Hg in area postrema lesion and sham lesion rats, respectively; chronic aortic catheter). Vascular strips from sham lesion-control rats. These changes in vascular reactivity also were observed in area postrema lesion-DOC-salt rats. DOC treatment in rats on a normal sodium intake did not result in hypertension or increased vascular reactivity. In summary, integrity of the area postrema is necessary for hypertension but not for changes in vascular reactivity, in DOC-salt rats. It appears that 1) changes in vascular reactivity may be necessary, but they are not sufficient to produce DOC-salt hypertension, and 2) if these vascular changes are secondary to a central nervous system effect, they are mediated by a pathway distinct from the area postrema.

Genetic association of hypertension and vascular changes in stroke-prone spontaneously hypertensive rats.

Isolated tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP) exhibit oscillatory contractile activity in response to norepinephrine, whereas those from normotensive Wistar-Kyoto rats (WKY) do not. To determine whether the norepinephrine-induced oscillations are related to high blood pressure or to separable genetic differences between strains, the response to norepinephrine was studied in adult SHRSP, WKY, and progeny of genetic crosses of SHRSP and WKY (F1, F2, F1 X SHRSP, F1 X WKY). Helical tail artery strips were mounted in a tissue bath for isometric force recording. Rats were classified as responders if oscillatory activity in the presence of 1.8 X 10(-7) M norepinephrine exceeded 250 mg/10 min (milligrams of force amplitude during a 10-minute interval). The blood pressures (mm Hg +/- SEM; tail cuff method) and percentage of rats exhibiting norepinephrine-induced oscillations were as follows: WKY: 109 +/- 3, 0%; F1: 129 +/- 4, 0%; F2: 150 +/- 4, 38%; F1 X WKY: 137 +/- 3, 9%; F1 X SHRSP: 188 +/- 7, 71%; SHRSP: 207 +/- 7, 100%. The distribution of the frequency of animals with oscillatory activity among the progenies was consistent with the hypothesis that a single gene locus determines the observed difference in oscillatory activity between the WKY and SHRSP strains. The allele from the SHRSP that determines the activity phenotype is recessive to the allele contributed by the normotensive WKY strain. In the segregating F2 progeny, the blood pressure of the responders was higher than that of the nonresponders (161 +/- 6 vs 144 +/- 4 mm Hg; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of felodipine on blood pressure and vascular reactivity in stroke-prone spontaneously hypertensive rats.

Isolated tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP), but not from normotensive Wistar-Kyoto rats (WKY), exhibit oscillatory contractions in response to norepinephrine. Previous studies indicate that the mechanism for these oscillations involves altered membrane calcium and/or potassium handling, and that this vascular change is a genetic defect associated with hypertension in SHRSP. The purpose of this experiment was to determine whether treatment of SHRSP with the calcium entry blocker felodipine would alter oscillatory activity. Adult SHRSP and WKY rats were treated orally with felodipine for 8 weeks. Felodipine treatment produced a significant decrease in blood pressure in SHRSP (control SHRSP: 240 +/- 7 mmHg, n = 6; felodipine-treated SHRSP: 164 +/- 8 mmHg, n = 5, P less than 0.05; tail-cuff method). Helically-cut tail artery strips from all rats were mounted in tissue baths for isometric force recording and exposed to norepinephrine (6 x 10(-9) to 6 x 10(-6) mol/l) for 20 min at each concentration. Oscillatory activity was defined as the sum of the magnitudes of all phasic contractions occurring during the final 10 min of norepinephrine incubation. Oscillatory activity was markedly reduced in tail arteries from felodipine-treated SHRSP when compared with control SHRSP. Felodipine also inhibited oscillatory activity when added directly to the tissue bath. It seems, therefore, that felodipine may lower blood pressure in SHRSP, at least in part, by correcting the genetic defect responsible for oscillatory activity.

Calcium influx and vascular reactivity in systemic hypertension.

Numerous studies have focused on functional vascular changes that characterize the hypertensive state. Recent evidence that suggests that increased vascular reactivity in hypertension is due to changes in the delivery of activator Ca++ through channels in the cell membrane will be reviewed. The primary evidence supporting this hypothesis comes from studies that characterize the effects of Ca++-free solution and calcium channel blockers on contractile properties of isolated vascular smooth muscle. In the present study, experiments were performed to investigate the role of Ca++ influx in vascular contractions produced by interventions that cause membrane depolarization. Isometric tension development in helical strips of carotid arteries from stroke-prone spontaneously hypertensive rats in response to elevated K+ and tetraethylammonium chloride was greater than that in carotid arteries from Wistar-Kyoto normotensive rats. The rate of tension development to K+-free solution in carotid arteries from stroke-prone spontaneously hypertensive rats was faster than in Wistar-Kyoto normotensive rat arteries. Contractile responses to all 3 depolarizing interventions were reduced in arterial strips incubated in Ca++-free solution containing the chelator ethylene glycol bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid and in arterial strips treated with the Ca++ channel blocker verapamil. These results are consistent with the hypothesis that constrictor stimuli that produce membrane depolarization cause an opening of Ca++ channels in the plasma membrane that are sensitive to the organic channel blockers. Further, a change in Ca++ permeability or membrane depolarizing mechanisms contributes to increased contractile responsiveness in carotid arteries of stroke-prone spontaneously hypertensive rats.

Effect of IgG-coated erythrocytes and lipopolysaccharide (LPS) tolerance on the depression of vascular reactivity caused by LPS.

Previous studies have shown that the injection of IgG-coated erythrocytes (EIgG) increased the mortality rate caused by bacterial lipopolysaccharide (LPS) and that animals made tolerant to LPS show a decrease in the mortality rate caused by LPS. The present study determined the effect of the injection of EIgG and of LPS tolerance on the depression of vascular reactivity caused by LPS in vivo or in vitro. For in vivo studies, LPS was injected intravenously into rats 2 h after the injection of E or EIgG. Aortae were removed 90 min after the injection of LPS, and cumulative concentration-response curves to phenylephrine were performed in helically cut aortic strips. LPS (.1 mg/kg) caused a 21% decrease in the maximum tension developed in response to phenylephrine in aortae from animals given erythrocytes. In contrast, animals given EIgG showed a 63% decrease in maximum tension following the injection of this dose of LPS. For in vitro studies, the depression of vascular reactivity caused by incubation with LPS of aortae from rats injected with EIgG was determined. As with the in vivo studies, there was a greater depression of vascular reactivity caused by incubation with LPS of aortae taken from animals injected with EIgG. Similar studies were carried out with rats made tolerant to LPS. Tolerance was induced by giving a regimen of five daily injections of LPS. Following the injection of LPS (1 mg/kg), the maximum tension of aortae from sham tolerant animals was depressed 63%, while aortae from LPS tolerant animals were depressed only 16%.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebroventricular infusion of angiotensin antagonist does not influence hypertensive response to blood-borne angiotensin II.

Blood-borne angiotensin II (AII) has several actions that result from interaction of the peptide with known AII-sensitive brain sites (i.e. circumventricular organs). In the rat, electrolytic ablation of the organum vasculosum of the lamina terminalis and surrounding periventricular hypothalamus, a known AII-sensitive area, will prevent development of hypertension in response to chronic intravenous AII infusion. The purpose of the present study was to determine if selective pharmacological blockade of brain AII receptors, rather than electrolytic lesion, would block chronic intravenous (i.v.) AII-induced hypertension. Male Sprague-Dawley rats were instrumented with chronic indwelling arterial and venous catheters and a lateral cerebroventricular cannula. In initial experiments, 5-day intracerebroventricular (i.c.v.) infusion of 1Sar,8Thr-AII (sarthran) at a dose of 1 microgram/h was found to produce functional blockade of central AII receptors with minimal effects on peripheral receptors (assessed by measuring the pressor responses to acute i.c.v. and i.v. AII administration). This dose of sarthran also had no agonistic effects in rats maintained on high sodium intake. Continuous blockade of brain AII receptors with i.c.v. sarthran had no effect on the ultimate development of hypertension seen in response to 5-day i.v. AII infusion (10 or 20 ng/min) coupled with high sodium intake. The failure of i.c.v. sarthran infusion to block chronic i.v. AII-induced hypertension probably reflects the inability of i.c.v. sarthran to gain access to a critical brain site(s) at which i.v. AII acts to cause increased arterial pressure.

Lack of effect of cerebellectomy on ascending dopaminergic neurons in the rat brain.

The dopamine content in striatum and substantia nigra of the rat was not altered 3 weeks after total or hemicerebellectomy. Furthermore, 3 days after hemicerebellectomy basal and haloperidol-stimulated activity of ascending mesolimbic and nigrostriatal dopaminergic neurons, as estimated from the in vivo rate of dopamine synthesis in striatum and nucleus accumbens, was not altered. Cupric silver degeneration staining following hemicerebellectomy failed to identify a direct anatomical pathway between cerebellum and substantia nigra in the rat.

The activity of rats in a swimming situation as a function of water temperature.

Previous research has shown that time before drowning in rats decreases gradually as stress is increased by varying water temperature in the swimming situation. In the present research, the activity of swimming rats appeared to be a U function of varying water temperature, lending support to the notion that activity is a behavioral measure that estimates the rats chances of survival in the water. This conclusion was further supported by the covariation of activity with a different behavioral measure of survival. In addition, activity during sessions decreased gradually, suggesting that a lowered activity is an adaptive response in the rat. Activity, thus, appears to be negatively correlated to the rat's survival chances under colder (14-23 degrees) and warmer (23-47 degrees) temperatures; i.e., in a more stressful situation, including extreme fear. It may be, therefore, that a decrease in activity obtained in present laboratory models (i.e., immobility) is more relevant to the extinction of fear than despair, as reported by other researchers.

Varying the temporal placement of a drinking opportunity in a fixed-interval schedule.

Three rats, lever pressing for food delivered on a fixed-interval 128-s schedule, were presented with a 16-s opportunity to drink from a retractable water source. The temporal placement of the water probe within the reinforcement cycle was varied sequentially, in steps of 16 s. Although the lever-pressing pattern was modulated by the intercalated water probe, water consumption during the probe itself was a decreasing function of time from the following reinforcer. These results were interpreted as evidence against the notion that schedule-induced drinking is a "ubiquitous" phenomenon and are congruent with results from other "intruded stimulus" experiments.

Effects of reinforcement rate and delay on the acquisition of lever pressing by rats.

The acquisition of lever pressing by naive rats, in the absence of shaping, was studied as a function of different rates and unsignaled delays of reinforcement. Groups of 3 rats were each exposed to tandem schedules that differed in either the first or the second component. First-component schedules were either continuous reinforcement or random-interval 15, 30, 60 or 120 s; second-component schedules were fixed-time 0, 1, 3, 6, 12, or 24 s. Rate of responding was low under continuous immediate reinforcement and higher under random-interval 15 s. Random interval 30-s and 60-s schedules produced lower rates that were similar to each other. Random-interval 120 s controlled the lowest rate in the immediate-reinforcement condition. Adding a constant 12-s delay to each of the first-component schedule parameters controlled lower response rates that did not vary systematically with reinforcement rate. The continuous and random-interval 60-s schedules of immediate reinforcement controlled higher global and first-component response rates than did the same schedules combined with longer delays, and first-component rates showed some graded effects of delay duration. In addition, the same schedules controlled higher second-component response rates in combination with a 1-s delay than in combination with longer delays. These results were related to those from previous studies on acquisition with delayed reinforcement as well as to those from similar reinforcement procedures used during steady-state responding.

Effect of antihypertensive therapy on a vascular change in genetically hypertensive rats.

Isolated tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP), but not normotensive Wistar-Kyoto (WKY) rats, exhibit oscillatory contractions in response to norepinephrine. To establish whether this vascular abnormality is secondary to elevated arterial pressure, SHRSP and WKY were treated with hydralazine and hydrochlorothiazide from weaning to 4 months of age. Hydralazine and hydrochlorothiazide treatment significantly attenuated hypertension development in SHRSP (systolic blood pressure: control SHRSP = 219 +/- 9 mmHg; treated SHRSP = 143 +/- 5 mmHg at 15 weeks of age). Helically-cut tail artery strips from all rats were mounted in tissue baths for isometric force recording and exposed to norepinephrine (6 x 10(-10)-6 x 10(-6) M) for 20 min at each concentration. Oscillatory activity was defined as the sum of the magnitudes of all phasic contractions occurring during the final 10 min of NE incubation. There was no significant difference in the magnitude of oscillatory activity between hydralazine/hydrochlorothiazide-treated SHRSP and control SHRSP. From these results we conclude that norepinephrine-induced oscillatory activity in SHRSP is a primary vascular abnormality that is not secondary to high blood pressure.

Hypertension during chronic peripheral and central infusion of angiotensin III.

Recent studies have suggested that the angiotensin II (ANG II) metabolite [Des-Asp]ANG II (ANG III) may be nearly equipotent with the parent compound in causing several acute neural responses known to be stimulated by angiotensin peptides (i.e., drinking, augmentation of sympathetic neurotransmission, and centrally mediated pressor responses). Because neural actions of ANG II are thought to contribute importantly to the ability of this hormone to cause chronic hypertension, the purpose of the present experiments was to explore the cardiovascular effects of chronic administration of ANG III either into the bloodstream or directly into the brain via the cerebral ventricles. The neurogenic component of the pressor response to acute infusion of ANG III also was reinvestigated. In anesthetized pithed rats (n = 6) ANG III had only 10% of the pressor potency of ANG II when given by acute (5-10 min) intravenous infusion. In conscious rats (n = 5) ANG III had 25% of the pressor potency of ANG II when tested using acute intravenous administration. The acute intravenous pressor potency ratio in conscious versus pithed rats was 4.8 for ANG III and 1.1 for ANG II, suggesting that, compared with ANG II, the pressor response to ANG III shows a greater dependence on neurogenic mechanisms at the doses tested. Chronic (5-day) intravenous infusion of ANG III (at 10, 20, and 100 ng/min) caused sustained hypertension without changes in fluid/electrolyte balance, but only at a dose (100 ng/min) estimated to produce blood levels of ANG III well beyond the "physiological" range.(ABSTRACT TRUNCATED AT 250 WORDS)

Suicidal behavior among patients in Bavarian mental hospitals.

The present research is a retrospective study to establish whether the number of suicides and attempted suicides has varied over two decades and which factors - size of the hospitals, patient admissions, physician and nursing personnel relationship with the patients, and forced admissions - are connected with such change. The analysis covers the decades 1950-1959 and 1967-1976. It was possible to establish a significant increase in attempted suicide and suicide during the second decade relative to the first one. The increase in suicide rate was observed in only three of the 10 investigated hospitals, while the attempted suicide rate increased in four hospitals. A relationship between number of beds and attempted suicide was observed only during the second decade and for suicide only in the first decade. In both decades forced admission had a significant influence on attempted suicide in contrast to suicide.

Neurohumoral contributions to chronic angiotensin-induced hypertension.

A central pressor effect of angiotensin II (ANG II) has been implicated in the pathogenesis of several forms of experimental hypertension. Therefore, the present studies were designed to investigate mechanisms that contribute to hypertension resulting from selective stimulation of brain ANG II receptors by chronic intracerebroventricular (ICV) infusion of ANG II. Specifically, the role of the sympathetic nervous system, the pressor actions of vasopressin, and the direct vasoconstrictor effect of blood-borne ANG II were investigated in rats made hypertensive by 5- to 7-day ICV ANG II infusions (6 micrograms/h). Rats were chronically instrumented with indwelling arterial and venous catheters and a lateral cerebral ventricular cannula. Acute intravenous infusion of the competitive ANG II receptor antagonist [Sar1-Ala8]ANG II during the period of ICV ANG II infusion resulted in a moderate decrease in arterial pressure, indicating that an increase in blood-borne ANG II may account for a small component of the hypertensive response to ICV ANG II. Activation of the sympathetic nervous system appeared to be the major contributor to the elevated arterial pressure, since acute ganglionic blockade and combined alpha- and beta-adrenergic blockade produced greater depressor responses in rats made hypertensive with chronic ICV ANG II infusion than in normotensive rats. Furthermore, peripheral sympathectomy delayed hypertension development. Intravenous administration of a specific antagonist of the vascular vasopressin receptor did not cause a depressor response in rats made hypertensive with chronic ICV ANG II infusions. These studies demonstrate that a major mechanism involved in the pressor response to acute ICV ANG II injections, namely vasopressin release, does not appear to contribute to hypertension produced by chronic ICV infusions of ANG II. Rather, this form of hypertension is characterized predominantly by an increase in sympathetic vasoconstrictor tone and possibly by a mechanism activated by a small increase in circulating levels of ANG II.

Increased vascular reactivity to Bay K 8644 in genetic hypertension.

These experiments compared potential-operated calcium channel function in smooth muscle from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Carotid artery strips from adult male SHRSP and WKY rats were suspended in tissue baths for isometric force recording. Contractile force was expressed as percent of response to 100 mmol/l KCl. Vascular strips from SHRSP were more sensitive to KCl (ED50 = 25 mmol/l) compared to strips from WKY rats (ED50 = 37 mmol/l). The calcium channel agonist Bay K 8644 (2.8 x 10(-10) to 2.8 x 10(-7) mol/l) produced tonic contractions in carotid artery strips from SHRSP (34% of the contractile response to 100 mmol/l KCl) but not in those from WKY rats. Incubation of vascular strips in 1.8 or 6 x 10(-10) mmols/l norepinephrine did not alter the maximal contractile response to Bay K 8644 in either strain of rats. In 12 mmol/l KCl, the maximal contractile response to Bay K 8644 was increased in both SHRSP (71%) and WKY rats (25%). In 18 mmol/l KCl, maximal contractile responses to Bay K 8644 in the two strains were similar (SHRSP = 73%, WKY = 76%). Removal of the endothelium did not significantly affect contractile responses to Bay K 8644 in either strain of rats. There were no differences in contractile responses to the calcium ionophore A23187 or in nifedipine-induced relaxation of potassium-activated vessels between carotid arteries from SHRSP and WKY rats. In summary, these results suggest that a difference in voltage-operated calcium channel function may underlie the increased sensitivity of SHRSP vascular smooth muscle to depolarizing stimuli.

Effect of inhibition of central angiotensin pressor mechanisms on blood pressure in spontaneously hypertensive rats.

The present experiments were designed to elucidate the role of central angiotensin II (AII) mechanisms in maintenance of established hypertension in adult spontaneously hypertensive rats (SHR) by determining the blood pressure response to chronic intraventricular (i.v.t.) infusion of the converting enzyme inhibitor teprotide or the AII receptor antagonist 1sar,8Thr-AII (sarthran). Male SHR (240-300 g) were given chronic indwelling arterial and venous catheters and bilateral lateral cerebral ventricular cannulae. The acute pressor responses to successive intravenous infusions of AII (sarthran experiments) or angiotensin I (AI; teprotide experiments) and to an intraventricular bolus injection of AII or AI were determined in the conscious rats. A 5-day intraventricular infusion of sarthran (1 or 6 micrograms/h) or teprotide (10 micrograms/h) in isotonic saline was maintained by subcutaneously implanted osmotic minipumps, and pressor responses were retested on the 5th day of intraventricular infusion. Five-day intraventricular sarthran infusion at 1 and 6 micrograms/h reduced the pressor response to intraventricular AII by 48 and 74%, respectively, while intraventricular teprotide (10 micrograms/h) inhibited the pressor response to intraventricular AI by 25%. None of the intraventricular infusions significantly decreased pressor responsiveness to intravenous AII or AI. In separate groups of SHR, tail-cuff blood pressure was monitored before, during, and after a 1-week intraventricular teprotide infusion (10 micrograms/h) or successive intraventricular infusions of sarthran at 1 microgram/h for 2 weeks followed by 6 micrograms/h for 1 week. Neither chronic intraventricular sarthran or teprotide caused a significant lowering of blood pressure in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Sodium-dependent hypertension produced by chronic central angiotensin II infusion.

Experiments were performed to characterize the hypertension produced by chronic intracerebroventricular (ICV) infusion of angiotensin II (ANG II) in conscious rats. Infusion of ANG II into a lateral cerebral ventricle for 5 days (1 or 6 micrograms/h) produced dose-dependent increases in mean arterial pressure associated with increased water intake. No consistent changes in heart rate, urinary electrolyte excretion, or water balance were observed. Similarly, no alterations in plasma sodium and potassium concentration, plasma osmolality, or plasma ANG II levels were seen during ICV ANG II infusion. Controlling fluid intake at 40 ml/day did not alter the development of hypertension in this model. Hypertension was found to be sodium dependent, with high sodium intake augmenting the increase in arterial pressure in response to chronic ICV ANG II. Although plasma aldosterone concentrations were increased in some situations during ICV ANG II infusion, adrenalectomy failed to alter the course of hypertension. This study demonstrates that chronic selective stimulation of brain ANG II receptors by means of continuous ICV infusion of ANG II produces sodium-sensitive increases in arterial pressure associated with, but not dependent on, increased fluid intake. This form of hypertension cannot be attributed to sodium and water retention, elevations in plasma aldosterone, or leak of significant amounts of ANG II from cerebrospinal fluid into the peripheral circulation.