Patricia Ruiz

The Renin-Angiotensin System in Different Stages of Spontaneous Hypertension in the Rat (S H R)

The present study analyzed the concentration of renin-like activity and angiotensinogen concentration (AoC) in different brain areas related to cardiovascular control in SHR and Wistar Kyoto (WKY) animals. Male rats of both strains were studied at 8, 16 and 30 weeks of age. The following brain areas were isolated: anterior, medial and posterior hypothalamus, septal area, periaqueductal gray (PG) and the remaining brain stem; nucleus tractus solitarius (NTS) and the remaining medulla oblongata. Plasma renin activity (PRA) and plasma and cerebrospinal fluid (CSF) AoC were determined. Renin-like concentration was higher in SHR than in WKY in the anterior hypothalamus, PG and NTS at different stages of hypertension development. AoC was also higher in some areas of the SHR brain during different periods. PRA, plasma and CSF angiotensinogen concentration showed significant differences between both strain of rats during the development of high blood pressure. Present data support the possibility that the central and peripheral renin-angiotensin system may participate in the maintenance of high blood pressure in the SHR animals.

The Brain Renin—Angiotensin System and the Development of Doc - Salt Hypertension

UNLABELLED The effect of captopril, given in the drinking fluid, on the development of DOC-salt hypertension was analyzed. Although captopril did not prevent an increase in blood pressure (BP) elicited by DOC-salt, captopril did diminish BP in both DOC-salt and control animals. From the first week of treatment DOC-salt rats increased their fluid intake (FI). At the end of the experiment, captopril reduced this increment (655% to 357%). At the same time plasma angiotensinogen was diminished (-35%; p less than 0.001) and cerebrospinal fluid (CSF) substrate concentration increased (+33%; p less than 0.02) in DOC-salt rats, captopril did not modify these changes. In control rats captopril did not alter FI, depleted plasma angiotensinogen, (-73%; p less than 0.001), did not change the central prohormone and increased plasma renin activity (PRA) (+260%; p less than 0.001). IN CONCLUSION CSF angiotensinogen concentration changes as previously found in CNS while a clear dissociation between plasma and CSF angiotensinogen was found in DOC-salt rats. In these animals the hypertension was not clearly affected by captopril treatment. However the effect of the converting enzyme inhibitor suggests that the central renin-angiotensin system could participate in the increase in FI.

Effect of EXP 3174 on Blood Pressure of Normoreninemic Renal Hypertensive Rats

This study examined the effect on mean blood pressure of a new orally active nonpeptide angiotensin II (Ang II) receptor antagonist, EXP 3174, in doses that completely block exogenous Ang II action. Anesthetized and conscious two-kidney, two clip chronic renovascular hypertensive rats and sham-operated animals were used. In anesthetized hypertensive rats, intracerebroventricular administration of the inhibitor had no effect on blood pressure, whereas blood pressure was normalized by intravenous injection of the antagonist (163 +/- 12 to 110 +/- 9 mm Hg, P < .05). In sham anesthetized rats, intravenous injection of EXP 3174 also lowered blood pressure (112 +/- 6 to 96 +/- 6mm Hg, P < .05). In conscious rats, intravenous EXP 3174 induced a fall in pressure that was larger in hypertensive (156 +/- 9 to 132 +/- 5 mm Hg, P < .05) than in sham (104 +/- 3 to 94 +/- 4 mm Hg, P < .05) rats. Plasma renin activity was very high in anesthetized animals (hypertensive versus sham, 87.8 +/- 8.3 versus 95.7 +/- 10.2 ng Ang I/mL per hour); differences were not significant either between anesthetized hypertensive and sham or in conscious animals (hypertensive versus sham, 9.42 +/- 1.58 versus 6.74 +/- 2.32 ng Ang I/mL per hour). Angiotensinogen concentration was higher in cerebrospinal fluid in anesthetized hypertensive rats (36.4 +/- 3.0 versus 26.0 +/- 2.4 ng Ang I/mL, P < .05) and in the artery wall of hypertensive conscious rats (103.1 +/- 10.3 versus 75.2 +/- 7.8 ng Ang I/g, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence of Early Structural Change in the Artery Wall of Two-Kidney One-Clip Goldblatt Hypertensive Rats

Vascular structural changes were studied during the development of two-kidney one-clip renal hypertension. The weight of the arteries and the concentration and total amount of ribonucleic acid, deoxyribonucleic acid, alkali-soluble proteins, collagen and elastin of the vascular wall were measured. Tritiated thymidine uptake was also determined 15 and 30 days after clipping. Hypertension developed in 58% of the animals while the rest remained normotensive. A significant increase in artery weight and in the total amount of nucleic acids and proteins was found in hypertensive rats. The uptake of 3H thymidine by the arteries of hypertensive rats was significantly increased 15 days after clipping. This increment showed a significant correlation with blood pressure levels. Present data seem to indicate that the increase in vessel wall dimensions observed is partly due to an increase in the number of smooth muscle cells during the acute phase; this alteration appears to be mainly due to the rise in blood pressure.

Angiotensin - Forming Enzyme Active at the Physiological PH in the Brain of Normal and Nephrectomized Rats

Enzymatic activity generating angiotensin at pH 5.5 and 7.2 has been detected in different areas of the central nervous system (CNS) of the rat. Control animals and those subjected to bilateral nephrectomy 48 h before the experiment (Nx) were analyzed. The different areas of the CNS were studied by the incubation of tissue homogenates in the presence (enzyme concentration) or not (enzyme activity) of an excess of added angiotensinogen. Concentration was determined by incubation at pH 7.2 and 5.5 while activity was evaluated only at pH 7.2. The enzymatic renin-like concentration at both pHs did not change after Nx thus showing they do not depend on plasma and vascular renin. On the other hand the activity of the enzyme showed a significant increase in the cerebral cortex and cerebellum after Nx suggesting an increased concentration of renin substrate and/or different concentrations of inhibitors or activators of the enzymatic system in those areas.

Renin-Like Activity in Vascular Tissue of Doc-Salt Hypertensive Rats

The presence of isorenin active at the physiological pH was investigated in DOC-salt hypertensive rats. The effect of chronic captopril treatment was analyzed in similarly treated animals and in control rats. The levels of the plasma (PRA) and vascular enzyme (VRLA) were compared with those of untreated control animals. DOC-salt administration was maintained during 4 or 8 weeks. Captopril was given in the drinking fluid beginning 4 days before DOC-salt treatment. Renin-like activity was measured in the aorta and mesenteric arteries. DOC-salt treatment reduced PRA to almost undetectable levels while aorta renin-like enzyme only decreased to 50% at 4 weeks and was not changed at 8 weeks. Isorenin levels in the mesenteric artery did not show any significant variation. Captopril did not prevent the increase in blood pressure due to DOC-salt administration and it induced a significant increase in PRA and in VRLA in control rats whereas it did not increase either - enzyme in DOC-salt treated rats. In summary these results confirm the existence of a vascular isorenin and suggest that both binding and local synthesis of the enzyme could take place in the arterial wall.

Effect of Central Norepinephrine Depletion on Renovascular Hypertension and on the Renin System

Some reports have stated that central norepinephrine (NE) depletion inhibited the development of hypertension in the rat. On the other hand, this pharmacological treatment induces changes on the central renin-angiotensin system. The present study was designed to follow the development of 2 kidney-2 clip (2k-2c) renovascular hypertension in rats depleted of central NE and to analyze the central and peripheral renin-angiotensin system. Male Wistar rats (n = 40) were used. Half of the animals was injected, intracisternally, with 6-hydroxydopamine (6-OHDA), the remaining rats only received the vehicle. One week later a silver clip was placed on each renal artery on half of the 6-OHDA treated rats and on half of the vehicle treated animals. A sham operation was performed on the remaining rats. Blood pressure was measured weekly during 7 weeks. Then, blood and cerebrospinal fluid (CSF) samples were obtained. The brain was dissected in several areas. NE and angiotensinogen concentration (AoC) were determined in tissue samples. AoC was evaluated in plasma and CSF; plasma renin activity was also measured. Hypertension development was not prevented by central NE depletion, which was significant in all central areas (p < 0.001). Other significant results showed that renal ischemia and/or NE depletion induced a significant increase in angiotensinogen concentration in the hypothalamus (p < 0.01) and in CSF (p < 0.05). In summary: central NE depletion was not able to modify the development of 2 k - 2 c hypertension. Treatment and renal ischemia induced an increase of central AoC.

The central and peripheral renin-angiotensin and noradrenergic systems in the spontaneous hypertensive rats (SHR)

The aim of this study was to evaluate the components of the renin-angiotensin system in the periphery and in the central nervous system (CNS) of the spontaneous hypertensive rats (SHR). On the other hand, the norepinephrine (NE) content of the different areas and of the mesenteric artery were also measured. Sixteen SHR and 9 Wistar Kyoto (WKY) control animals were used at about 6 months of age. Blood and cerebrospinal fluid (CSF) samples were collected. The brain was dissected into several areas and the mesenteric artery was excised. Plasma renin activity (PRA), plasma angiotensinogen concentration (P1AoC), brain renin (RC) and angiotensinogen concentrations (AoC) were evaluated by radioimmunoassay. NE was determined in all the tissues by a fluorimetric technique. PRA, P1AoC and NE concentration in the mesenteric artery were similar in both groups. An increase in the NE content of the cerebellum was detected in the SHR without changes in the other areas of the CNS. AoC was decreased in the CSF and in the brain stem of the SHR animals. RC was evaluated in the hypothalamus, brain stem, cerebral cortex and cerebellum of the same strain of rats. These results seem to indicate the some alteration of the peptidergic system in the CNS is present in the hypertensive animals.

Vascular renin-like activity in aorta and mesenteric artery of the rat

Vascular renin-like enzymatic activity (VRLA) has been measured in the artery wall of control and experimental rats. The following groups have been studied: 1-normal salt diet; 2-high salt diet; 3-low salt diet; 4-bilateral nephrectomy (Nx); 5-sham operated for Nx. VRLA was evaluated in the aorta (ARLA) and in the mesenteric arteries (MRLA). Blood samples were obtained for plasma renin activity (PRA) determination. High salt diet decreased PRA, ARLA and MRLA whereas low salt diet increased PRA, did not change ARLA and decreased MRLA. PRA was almost undetectable in Nx animals while ARLA showed a 40% reduction and MRLA was unchanged in these animals. These results would indicate that the changes in PRA induced different variations in the renin-like content of the aorta and the mesenteric artery. The differences could be mainly due to two factors: 1) the capacity of the vascular tissue to bind circulating renin and 2) the capacity of each tissue to synthetize renin-like material in situ.

Vascular Structural Changes in the Artery Wall of Unilateral Nephrectomized Rats

Wet and dry weight, concentration and total amount of nucleic acids and proteins, and incorporation of tritiated thymidine were measured in the arteries of rats after 7 and 15 days of unilateral nephrectomy, sham operation and in control animals. Arteries of uninephrectomized rats showed increased wet and dry weight, increased DNA and protein content after 7 and 15 days and a higher rate of tritiated thymidine uptake after the first week. These results suggest an early proliferative process in the arteries of unilateral nephrectomized rats.