An anteroventral third ventricle (AV3V) lesion in the brain prevents several forms of experimental hypertension. The present experiment was designed to determine whether the AV3V lesion prevents NaCl-induced hypertension in Dahl salt-sensitive (S) rats and whether attenuation of vasopressin release reported in lesioned rats contributes to the protective effect of the AV3V lesion against hypertension. After the AV3V lesion Dahl S rats received daily injections of either vasopressin (pitressin tannate, 500 mU/kg) or vehicle during 10 wk of 8% high-NaCl diet. Sham-lesioned rats served as controls. The blood pressure in sham-lesioned rats receiving vehicle was 189 mmHg after 10 wk of high-NaCl diet. Lesioned rats given vehicle showed a significantly smaller increase in blood pressure than sham-lesioned rats (P less than 0.001), the blood pressure averaging 161 mmHg at 10 wk. Lesioned rats given vasopressin also showed a smaller increase in blood pressure than sham-lesioned rats (P less than 0.05), but the final blood pressure averaged 176 mmHg and was significantly higher than that of lesioned rats given vehicle (P less than 0.025). Vasopressin injections corrected the hypernatremia in lesioned rats. In another experiment the effect of the AV3V lesion on the renal papillary plasma flow (RPPF) in Dahl S rats was studied. Dahl S rats have a lower RPPF than Dahl salt-resistant (R) rats even on a low-NaCl intake. The AV3V lesion increased the RPPF by 14% in S rats (P less than 0.025). These findings suggest that NaCl-induced hypertension in Dahl S rats requires the integrity of the AV3V region for its full expression, and the ability of the AV3V lesion to attenuate the NaCl-induced hypertension in Dahl S rats is partly related to the attenuation of vasopressin release. Moreover, the AV3V lesion partly corrected one of the characteristic features of Dahl S rats, the reduction in RPPF, when compared with Dahl R rats, with both strains on a low-NaCl intake.

Three experiments were carried out to determine whether atrial natriuretic factor (ANF) plays a part in Dahl hypertension. Results showed that ANF from both atria from 13 Dahl salt-sensitive (S) rats that had been fed a 4% NaCl diet for 12 weeks induced an average peak Na excretion of 23.0 muEq/min/g kidney in 13 Sprague-Dawley (SD) recipients vs 12.6 from atria from 13 salt-resistant (R) rats fed 4% NaCl (-45%, p less than 0.01), possibly indicating greater ANF secretion in S rats in order to enhance a reduced Na excretion. In 13 R rats, the ANF content in both atria increased from 14.0 after a 0.11% NaCl diet to 23.7 after 5 days of 4% NaCl diet (p less than 0.001) and then back to 12.6 after 12 weeks of 4% NaCl (p less than 0.001). Thus, ANF almost doubled after brief Na loading but returned to normal during continued Na loading. In S rats with a tendency to Na retention, ANF was elevated to about 23 in all three periods. ANF produced a 130-fold increase in natriuresis and a renal papillary plasma flow ( RPPF ) of 30.8 ml/min/100 g, 41% above the control level of 21.7, p less than 0.001. The marked increase in RPPF is very likely a partial cause of the natriuresis. A constant amount of ANF was continuously infused intravenously into 10 S rats and nine R rats all on 0.11% NaCl diets. Mean Na excretions in R and S were 5.3 and 4.6 muEq/min/100 g kidney before ANF.(ABSTRACT TRUNCATED AT 250 WORDS)

The relative roles of renal pressor and antihypertensive factors in the pathogenesis cf experimental renal hypertension remain a central, and disputed, issue.In our laboratory, we have evolved two strains of rats with opposite genetic predispositions to different forms of experimental hypertension including those produced by salt and unilateral renal artery constriction (1-4). But when a rat from each of the two strains was united in parabiosis, it was found that the reaction pattern to salt hypertension could be changed, i.e., the normally resistant animal not only developed significant hypertension but did so prior to its susceptible partner (5). This was interpreted to indicate that the genetic factors might act via a humoral agent, transmittable between rats from the two strains. The studies did not settle whether such factors were of a pressor or anti-pressor nature.In the current study, we have explored the effects of a variety of renal manipulations in single and parabiotic animals. Our results suggest that, although intact renal tissue has an antihypertensive action, the loss of this function is not alone sufficient to explain renal hypertension; a pressor agent must be involved. Since only animals from the sensitive strain were able to induce experimental hypertension in their intact parabiotic partners, we have speculated that, in animals from the sensitive strain there are two pressor principles: One agent is present in animals from this strain as well as in the one resistant to hypertension and is not transmitted through the parabiosis junction; a second agent is peculiar to the strain predisposed to hypertension and will traverse the junction. Material and MethodsThe rats belonged to two strains developed in this laboratory, called R and S because of their resistance or sensitivity, respectively, to experimental hypertension.

SUMMARY Kidney prostaglandlns appear to bare powerful Influences on Nad-Induced hypertension. In quick-frozen kidneys, the concentration of prosUglandin E, (PGE,) in the renal papilla is 60% lower in Dahl S rats than in Dahl R rats (17 ng/100 mg TS 42 ng/100 mg,p < 0.01) when both S and R rats are fed a 0.3% low NaCI diet. When S and R rats eat a 4% high NaCl diet for 4 weeks or 11 weeks, the PGE, concentration doubles in both strains (p < 0.05) but the papillary PGE, concentration in the S rats is always about half that in the R rat (p < 0.01). Through effects on sodium (Na) excretion and papillary plasma flow, the low PGE, in S papillae may account in part for the large rises in the blood pressure (BP) of S rats after eating a high NaCI diet. This proposition was explored by utilizing high fat diets with either normal or high linoleic acid content. Arachidonic acid is the precursor of PGE, and linoleic add is the precursor of arachidonic acid. It turned out that the low PGE, level in S papillae could be tripled by a diet high in linoleic acid. Sixteen S rats on a 16-week diet of 5% NaCI and 1.5% linoleic acid had a mean papillary PGE, level of 30 compared to a level of 89 in 15 other S rats on a diet of 5% NaCI and 16% linoleic acid. The 16% high linoleic diet tripled the PGE, concentration in S papillae (p < 0.005). It also increased the PGE, concentration in R papillae Vh times, 137 vs 53 (p < 0.02). In rats on either high or normal linoleic diets, the PGE, In S papillae was always at least 35% less than that in R papillae. However, the 16% high linoleic diet did raise the papillary PGE, level In S rats up to that found in normal rats on regular rat chow of equivalent NaCI content. Moreover, this change in PGE, level was associated with greatly reduced BP rises in S rats. The BP of S rats on a 5% NaCI-1.5% linoleic diet began to rise after 5 weeks on the diet and reached 183 mm Hg after 16 weeks. The BP of S rats on a 5% NaCl-16% linoleic diet did not begin to rise until 12 weeks on the diet and reached only 166 after 16 weeks. The high linoleic diet greatly delayed the onset of the rise in BP and significantly reduced the ultimately attained level (p < 0.001). In fact, on a low 0.3% NaCI diet, S rats of comparable age reached approximately the same mildly hypertensive level of 166. Thus, in S rats, the high linoleic diet brings papillary PGE, up to normal and also prevents the large rises in BP usually related to a high NaCI Intake. These two changes may well be causally related. 1 Life-long low-salt diets can prevent hypertension even in susceptible individuals.1 ' Diets very low in sodium can reduce the blood pressure (BP) in established hypertension. Drugs such as thiazides, which slightly reduce body Na content, can do the same. On the other hand, very high intakes of NaCI can raise BP in humans.*" 11The way in which Na affects the BP in humans is still not completely understood. To approach this question, we have made some observations in the two From the

Catecholamine levels and activity of catecholamine-forming enzymes have been quantitated in adrenal glands of Dahl sodium-resistant (R) and sodium-sensitive (S), genetically hypertensive rats maintained on low- or high-salt diets. A high-salt diet results in markedly different changes in the catecholamine metabolism in R and S rats. In R rats, a high-salt diet reduces the activities of tyrosine 3-hydroxylase (TH;-5%) and dopamine beta-hydroxylase (DBH; -18%) as well as the levels of all catecholamines (dopamine -28%, norepinephrine -11%, and epinephrine -28%). In contrast, S rats fed a high-salt diet showed increased TH (+7%) and phenylethanolamine N-methyltransferase (+16%) activities as well as an increased content of adrenal norepinephrine (+13%) and epinephrine (+21%). These findings demonstrate a genetic difference in the effects of a high-salt diet on the synthesis of catecholamines in the adrenal gland of Dahl R and S rats. Hypertension only occurs in S rats on a high-salt diet, concomitant with large increases in the formation of adrenal catecholamines.