Philip G. Baer

Comparison of effects of prostaglandins E2 and I2 on rat renal vascular resistance

Effects of PGE2 and PGI2 on renal vascular resistance (RVR) were compared in anesthetized rats. Renal blood flow and systemic blood pressure were measured before and during infusion of PGE2 (2--2 microgram/min) or PGI2 (1--5 microgram/min) into the aorta just proximal to the renal arteries. Both prostaglandins significantly decreased blood pressure and renal blood flow, but effects on RVR were dissimilar. At low doses, PGI2 reduced RVR in 8 of 10 rats; PGE2 increased it in 5 of 7. At higher doses, PGE2 increased RVR in all rats; during PGI2 infusion RVR did not significantly exceed control at any dose. We conclude that, in the intact rat, PGE2 increases RVR either directly or through potentiation of other constrictor stimuli, while PGI2 tends to reduce RVR and diminish the renal response to other constrictor stimuli. PGI2 is the only prostaglandin found to decrease RVR in the rat.

Renal denervation at weaning retards development of hypertension in New Zealand genetically hypertensive rats.

The development of hypertension was studied in 3 to 13-week old New Zealand genetically hypertensive (NZGH) rats subjected to bilateral renal denervation (D) or sham operation (S) at 4 weeks of age. Denervation retarded the development of hypertension and delayed the establishment of stable hypertension; blood pressure of D-NZGH rats was 15–40 mm Hg lower than that of S-NZGH rats from 3 to 7 weeks after surgery, but was similar in the two groups thereafter. D-rat renal catecholaimine content was reduced to 17% of control at 1 week after surgery; by the fourth week post surgery, renal catecholamine content had risen to 40% of control, and blood pressure of the D-group had begun to rise, suggesting that spontaneous renal reinnervation prevented the antihypertensive effect of renal denervation from being a permanent one. During the period when blood pressure of the S-rats was greater than that of the D-rats, urinary sodium excretion of the two groups was not significantly different, suggesting that over this interval the relationship between blood pressure and urinary sodium excretion shifted to the right along the pressure axis in the S-rats but not in the renal-denervated rats. Throughout the 60-day period of observation, urinary excretion of prostaglandin E2 and kallikrein did not differ between the renal-denervated and sham-operated rats. (Hypertension 4: 361–368, 1982)

Bilateral renal denervation can prevent the development of stress-induced hypertension in the borderline hypertensive rat

The borderline hypertensive rat (BHR) shows large blood pressure responses to either stress or a high salt diet. Since the renal nerves have been shown to play a role in several animal models of hypertension, the current study sought to determine the effect of bilateral renal denervation on the development of stress-induced hypertension in the BHR. BHR were deprived of renal nerves under ether anesthesia after either 5 or 11 weeks of daily 2-hour stress sessions. Additional BHR received sham surgery. Unstressed BHR, age-matched to stressed groups, received denervation or sham surgery. Following a 3 week recovery period, the protocol (stress or no stress) was continued for 10 additional weeks. Tail cuff systolic blood pressures were obtained weekly. BHR stressed for 5 weeks prior to denervation failed to develop hypertension in response to continued stress. Although BHR stressed for 11 weeks prior to denervation showed a temporary reduction in pressure following denervation, blood pressure returned to the hypertensive levels of sham-operated controls after several weeks. Thus, there may be a critical period during which the renal nerves are necessary for the expression of stress-induced hypertension in the BHR. These observations are discussed in relation to the effects of renal denervation on hypertension in various animal models.

The contribution of prostaglandins to renal blood flow maintenance is determined by the level of activity of the renin-angiotensin system.

Abstract A growing body of experimental and clinical evidence has led to the formation of the hypothesis that the contribution of intrarenal prostaglandins to the determination of renal blood flow is a function of the level of activity of renin-angiotensin system. The following is a brief review of a portion of the pertinent literature. The focus of this review is the effect of inhibition of prostaglandin synthesis on renal blood flow in diverse conditions characterized by increased activity of the renin-angiotensin system, including reduction of renal arterial pressure, ureteral obstruction, hemorrhage, the hepatorenal syndrome, and sodium depletion. Under these conditions, in contrast to the lack of effect in non-stress conditions, the renin-angiotensin system activity is high, and prostaglandin synthesis inhibition is associated with reductions in renal blood flow.

Estradiol is responsible for reduced renal prostaglandin dehydrogenase activity in female rats

The contribution of sex steroids to sex-related differences in renal prostaglandin dehydrogenase activity and urinary prostaglandin excretion was examined in 7-8-week-old male and female rats subjected to sham-operation or gonadectomy at 3 weeks of age. Rats were injected subcutaneously twice over a 6-day interval with vehicle (peanut oil, 0.5 mg/kg) or with depot forms of testosterone (10 mg/kg), estradiol (0.1 mg/kg), progesterone (5 mg/kg), or with estradiol and progesterone combined (0.1 and 5 mg/kg). After the second injection, 24-h urine samples were collected for prostaglandin measurement by radioimmunoassay; the rats were killed, and renal and pulmonary prostaglandin dehydrogenase activities were determined by radiochemical assay. Renal prostaglandin dehydrogenase activity was 10-times higher in intact male rats than in intact females. Gonadectomy increased renal prostaglandin dehydrogenase activity 4-fold in females, but had no effect in males; estradiol, alone or combined with progesterone, markedly suppressed renal prostaglandin dehydrogenase activity in both sexes, while testosterone or progesterone alone had no effect. Pulmonary prostaglandin dehydrogenase did not differ between the sexes and was unaffected by gonadectomy or sex-steroid treatment. Intact female sham-operated rats excreted 70-100% more prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha in urine than did males; gonadectomy abolished the difference in urinary prostaglandin E2 excretion. Estradiol decreased urinary prostaglandin E2 in females but not in males; treatment with other sex steroids did not alter urinary prostaglandin excretion.

Vasopressin Secretion in the New Zealand Genetically Hypertensive Rat

A study was undertaken to evaluate the role of vasopressin in the pathogenesis of hypertension in New Zealand genetically hypertensive (NZGH) rats. During the course of development of hypertension in NZGH rats from 4 to 11 weeks of age, the 24 h urinary excretion of vasopressin did not differ from that of the New Zealand normotensive control rats (NZNR). Furthermore, at the conclusion of the study (rats 13 to 14 weeks old), the plasma vasopressin concentrations in NZGH and NZNR rats were not significantly different. Although there was no evidence for a difference in secretion of vasopressin from the neurohypophysis in the NZGH rats, there was a substantially increased pressor responsiveness to vasopressin in these rats. This was not specific since NZGH rats also had an increased pressor responsiveness to angiotensin II. The importance of increased pressor responsiveness to vasopressin in the hypertensive process in the NZGH rat requires further study.

Reduced glandular kallikrein-like activity in the anterior pituitary of the new zealand genetically hypertensive rat

Anterior pituitaries of New Zealand genetically hypertensive and normotensive rats were compared for their content of glandular kallikrein-like activity. Anterior pituitary homogenates were assayed for their ability to cleave a chromogenic peptide substrate for glandular kallikrein (H-D-val-leu-arg-p-nitroanilide) at pH 8.0. Anterior pituitaries of both male and female New Zealand genetically hypertensive rats contained significantly less glandular kallikrein-like activity than their normotensive counterparts (-55% for females and -31% for males).

Adrenic acid inhibits prostaglandin synthesis

Abstract Adrenic acid inhibits oxygenation of arachidonic acid by homogenates of rabbit renal medulla and blunts the vascular effects of bolus injections of arachidonic acid in the rat. Adrenic acid may be a naturally occurring modulator of cyclo-oxygenase activity.

Differences in 15-hydroxyprostaglandin dehydrogenase activity in male and female rat kidneys.

Abstract In adult Wistar rats, 15-hydroxyprostaglandin dehydrogenase (PGDH) activity of male kidney homogenates was 40 times greater than that of female kidney homogenates; in contrast, PGDH activity of male and female lung homogenates did not differ significantly. Perhaps causally related to the difference in renal PGDH activity, urinary excretion of prostaglandin (PG) E2 by female rats was twice, and excretion of PGFα 3 times, that by males. Female rat renal homogenate and female rat renal high-speed supernatant inhibited PGDH activity of male rat renal homogenate and the activity of partially purified bovine PGDH.

Prostaglandin E2 metabolism by isolated kidneys of New Zealand genetically hypertensive and normotensive rats.

Abstract Metabolism of PGE2 by isolated, Krebs-perfused kidneys of New Zealand genetically hypertensive rats (NZGH) and New Zealand normotensive control rats (NZNR) was compared. The principal metabolite of PGE2 appearing in the renal venous effluent was 13,14 dihydro-15-keto PGE2. No difference was observed in the metabolism of exogenous PGE2 by isolated kidneys of the two strains, despite twofold higher levels of 15-hydroxyprostaglandin dehydrogenase activity in homogenates prepared from kidneys of NZNR than in those of NZGH rats.