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S Oparil

Publications and source records attributed to S Oparil.

360 records · Page 20Linked to original sources
PubMedDate not supplied

Regional myocyte size in normotensive and spontaneously hypertensive rats.

Regional differences in cell size in the hearts of rats with and without cardiac hypertrophy were studied using isolated muscle cells. Isolated cardiac myocytes were prepared from left ventricular free wall inner and outer halves and the right ventricle of six male 12-week-old spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Fischer-344 rats. In SHR, blood pressure was increased to 188 +/- 4 (SEM) mm Hg versus 143 +/- 2 and 133 +/- 10 for WKY and Fischer rats, respectively (p less than 0.001). Total heart weight was increased to 1103 +/- 29 mg in SHR compared to 824 +/- 21 in WKY and 951 +/- 23 in Fischer rats (p less than 0.001. Isolated cardiac myocytes were prepared by perfusion of isolated hearts with Ca++ free Hanks' solution containing EGTA followed by collagenase-containing media. Mean length, width and volume of 150 cells stained with hematoxylin and eosin from each site were measured with a sonic digitizer. Two nuclei were present in 85 to 87% of isolated cells from all strains and regions. There was no difference among strains in right ventricular cell length, width, or volume, nor between left ventricular inner and outer halves within each strain. Left ventricular cells were larger than right ventricular cells (p less than 0.05) in all strains. Left ventricular cells of SHR were larger than left ventricular cells of WKY of Fischer rats in proportion to the increase in total heart weight, indicating that cardiac enlargement in SHR is due to increased cell size rather than increased cell number.

Animals↗
PubMedDate not supplied

Importance of renal sympathetic tone in the development of DOCA-salt hypertension in the rat.

In many experimental models, acute increases in sympathetic nervous system activity produce disproportionately greater vasoconstriction in the renal vascular bed than occurs in most other vascular beds. Since increased sympathetic nervous system activity has been implicated in the pathogenesis of DOCA-salt hypertension in the rat, we hypothesized that an attenuation of renal sympathetic tone would delay the development of this form of hypertension. Renal denervation was carried out in 5-week-old uninephrectomized male Sprague-Dawley rats 1 week before beginning DOCA-salt treatment. Systolic blood pressures using the tailcuff method in 32 sham-operated rats were significantly (p less than 0.05) elevated above control by Day five (115 +/- 3 vs 128 +/- 3 mm Hg) of DOCA-salt administration and continued to rise, reaching a plateau by Day 21 (192 +/- 5 mm Hg). In contrast, DOCA-salt administration in 32 renal denervated rats did not result in a significant elevation of blood pressure above control until Day 17 (121 +/- 3 vs 135 +/- 3 mm Hg, p less than 0.05). During the first 2 weeks of DOCA-salt treatment, fractional urinary sodium excretion was significantly greater (p less than 0.05) in renal denervated rats than in sham animals. During the third week of DOCA-salt administration, renal denervated rats had a rapid rise in blood pressure and a fall in fractional urinary sodium excretion to the level of the sham-operated animals. Coincident with the development of hypertension was a threefold increase in renal norepinephrine content (5.3 +/- 0.4 ng/g on Day 14 vs 17.7 +/- 3.0 ng/g on Day 24, p less than 0.01), suggesting reinnervation. These data suggest that increased renal sympathetic tone in the DOCA-salt rat facilitates sodium retention and is necessary for the development of the hypertension.

Animals↗
PubMedDate not supplied

Hemodynamic response to vascular expansion following immunosympathectomy in spontaneously hypertensive rats.

Spontaneously hypertensive male rats (SHR) or normotensive Kyoto-Wistar (WKY) male rats underwent either sham or nerve growth factor antiserum (NGFAS) treatment during the first week of life. The NGFAS treatment prevented the development of hypertension in SHR but did not prevent the development of left ventricular groups in vivo under general anesthesia. After the recording of resting parameters, homologous whole blood was transfused until the rise in cardiac output reached a plateau. At rest, LV systolic pressure of the NGFAS-treated SHR was significantly lower than that of the sham-treated SHR and not statistically different from that of the WKY rat. The LV end diastolic pressures did not differ among the four groups. Both SHR groups had significantly lower cardiac, stroke, and contractility indices than di the WKY groups. Following vascular expansion, LV filling pressure, stroke index, and stroke work index rose in all groups. The response in the SHR was greater than that in WKY groups. Interestingly, the systolic pressure of the NGFAS-treated SHR rose to the same level as in the sham-treated SHR. Heart rate and calculated systemic vascular resistance fell following transfusion. The SHR appears to exhibit an altered response to increased filling pressure and increased afterload. Our findings are consistent with the concept of an alteration in the compliance of the LV in the SHR.

Animals↗
PubMedDate not supplied

Role of the renal nerves in the pathogenesis of one-kidney renal hypertension in the rat.

Increased sympathetic nervous system activity has been demonstrated in established one-kidney one clip hypertension in the rat. To determine the importance of the renal nerves in this model of hypertension, renal denervation or sham operation was carried out 2 weeks after clipping. Systolic blood pressure (BP) after clipping the renal artery in 27 uninephrectomized male Charles River rats increased significantly from 125 +/- 3 mm Hg to a stable level of 185 +/-7 mm Hg by 2 weeks, in association with a positive sodium balance. Renal denervation in 13 animals resulted in a significant decrease in BP to 137 +/- 7 mm Hg, while no change in BP was seen after sham operation in 14 animals. There was no difference in mean daily water intake, mean daily sodium intake, mean daily urine volume, or mean fractional urinary sodium excretion between sham-operation and renal-denervated animals during the 2 weeks after operation. Plasma renin activity (PRA) and creatinine clearance were not significantly different at sacrifice 2 weeks after operation. Six of the renal-denervated rats were followed for 11 weeks after surgery. The BP rose again to hypertensive levels (187 +/- 8 mm Hg) by 5 weeks after renal denervation. Repeat renal denervation resulted in a significant decrease to 142 +/- 8 mm Hg. Renal denervation in eight rats with established one-kidney Grollman hypertension (185 +/- 8 mm Hg) also resulted ina significant decrease in systolic BP (143 +/- 8 mm Hg). The data demonstrate the importance of intact renal nerves in the maintenance of hypertension in the one-kidney renal hypertensive rat. The depressor effect of renal denervation is not mediated by alterations in sodium intake or excretion, water intake or excretion, creatinine clearance or PRA.

Animals↗
PubMedDate not supplied

The role of calcium in the control of renin release.

The effects of removing external calcium and inhibiting entry of calcium into the cell by treatment with D-600 on renin release from renal cortical slices of male Sprague-Dawley rats were examined. Baseline renin release, angiotensin II (AII)-induced inhibition, and isoproterenol-induced stimulation of renin release were studied. Removal of external calcium by chelation with 5 mM EGTA inhibited basal renin release while treatment with 1 mM EGTA stimulated basal renin release slightly. Incubation of slices with zero calcium medium containing 1 mM EGTA had no effect on isoproterenol-induced stimulation of renin release. In contrast, similar treatment reduced the inhibitory effect of AII from 58.7% of baseline to 85.3% (p less than 0.001). Similarly, blockage of calcium entry into cells with D-600 had no effect on isoproterenol-induced stimulation of renin release but abolished AII-induced inhibition. Replacement of sodium in the bathing medium with choline had no effect on baseline renin release or on AII-induced inhibition of renin release, ruling out the possibility that D-600 altered renin release via an effect on sodium influx. Taken together, the data strongly suggest that AII-induced inhibition of renin release is partially dependent on the presence of external calcium but that isoproterenol-induced stimulation of renin release is not.

Angiotensin II↗
PubMedDate not supplied

Importance of the renal nerves in the pathogenesis of experimental hypertension.

Anatomical studies have demonstrated sympathetic innervation of the renal arterioles, juxtaglomerular apparatus, and renal tubules. Physiologic studies of the effects of the renal efferent nerves on renin release and renal sodium handling indicate that they play an important role in body fluid homeostasis and cardiovascular regulation. In addition, evidence is accumulating that stimulation of intrarenal mechanoreceptors and chemoreceptors causes in increase in renal afferent nerve activity and that alterations in renal afferent nerve traffic are, in turn, associated with changes in blood pressure and in vasoconstrictor tone in the contralateral kidney. Further, recent studies have demonstrated functionally significant connections between renal afferent nerves and the central nervous system. Interruption of the renal sympathetic nerves has been shown to prevent or attenuate hypertension in a number of animal models, suggesting that the renal nerves have an important role in the pathogenesis of experimental hypertension. In the spontaneously hypertensive rate of the Okamoto strain (SHR) and the DOCA-NaCl rat, the delay in the development of hypertension produced by renal denervation is due in part to increased sodium excretion thought to be secondary to interruption of the renal efferent nerves. In contrast, in one-kidney, one clip and two-kidney, one clip Goldblatt hypertension in the rat and coarctation hypertension in the dog, the depressor effect of renal denervation is unrelated to changes in urinary sodium excretion or plasma renin activity. In these models the attenuation of hypertension following renal denervation appears to be secondary to a decrease in peripheral sympathetic activity. Evidence in the one-kidney model suggests that interruption of the renal afferent nerves lower blood pressure via an effect on central noradrenergic mechanisms.

Afferent Pathways↗
PubMedDate not supplied

Central effects of prostaglandin E2 on blood pressure and plasma renin activity in rats. Role of the sympathoadrenal system and vasopressin.

This study was designed to determine the roles of the sympathetic nervous system, adrenal medulla, and arginine vasopressin (AVP) in mediating pressor and plasma activity (PRA) responses to intraventricularly (ICV) administered prostaglandin E2 (PGE2) in conscious rats. The ICV PGE2 elevated blood pressure and caused increases in PRA, plasma AVP, and plasma norepinephrine and epinephrine. The pressor effect of ICV PGE2 was not influenced by pretreatment with captopril, but was attenuated by the AVP antagonist, d(CH2)5Tyr(Me)AVP, and by phenoxybenzamine, and was completely abolished by the combination of the AVP antagonist and phenoxybenzamine. The PRA response to ICV PGE2 was not affected by bilateral renal denervation or by phenoxybenzamine alone, but was attenuated by propranolol alone and was completely abolished by the combination of propranolol and phenoxybenzamine. Bilateral adrenomedullectomy did not affect the pressor response to ICV PGE2, whereas it attenuated the increase in PRA and completely abolished the increase in plasma epinephrine. These results suggest that the pressor effect of ICV PGE2 is the result of increased sympathetic nervous system activity and is dependent on the stimulation of alpha-adrenergic receptors and on AVP release. The pressor response to ICV PGE2 is accompanied by but not dependent on an increase in PRA. The renin-stimulating effect of centrally administered PGE2 is, at least in part, dependent on beta-adrenergic receptor stimulation by increased circulating catecholamines.

Adrenal Medulla↗
PubMedDate not supplied

Role of the renal nerves in the maintenance of DOCA-salt hypertension in the rat. Influence on the renal vasculature and sodium excretion.

We previously observed that the renal nerves facilitate sodium retention and contribute to the development of DOCA-salt hypertension in the rat. To determine whether the renal nerves also participate in the maintenance of DOCA-salt hypertension, we studied the effects of renal denervation after 3 or 10 weeks of DOCA-salt treatment on systolic blood pressure, urinary sodium excretion, creatinine clearance, and precapillary arteriolar wall/lumen ratios of renal, hindlimb muscle, and cremaster muscle vascular beds. Systolic blood pressures of animals given DOCA-salt reached a plateau by 3 weeks of treatment at which time a sham operation or renal denervation was performed. Sham operation in hypertensive animals resulted in no change in systolic blood pressure and no change in percent sodium intake excreted. Wall/lumen ratio of the renal precapillary arteriole in sham-operated hypertensive animals was increased compared to similar sized vessels in hindlimb and cremaster muscle. In contrast, renal denervation resulted in a natriuresis and an attenuation of the hypertension (208 +/- 7 mmHg; p less than 0.01). Wall/lumen ratio of the renal capillary arterioles in renal denervated animals was no different than similar sized vessels in hindlimb and cremaster muscle and significantly less than that seen in sham-operated animals (0.85 +/- 0.05 vs 1.03 +/- 0.06; p less than 0.05). In another group of animals, sham operation or renal denervation was performed after 10 weeks of DOCA-salt treatment. At this time neither operation altered systolic blood pressure or sodium balance. In contrast to 3-week DOCA-salt-treated hypertensive sham-operated animals, renal precapillary arteriolar wall/lumen ratio of 10-week animals was no different than similar sized vessels in hindlimb and cremaster muscle. In addition, renal precapillary arteriolar wall/lumen ratio of 10-week DOCA-salt-treated renal-denervated animals was no different than that seen in 10-week DOCA-salt-treated sham-operated hypertensive animals. Creatinine clearance of the 10-week DOCA-salt-treated sham-operated or renal-denervated animals was significantly (p less than 0.01) lower than that of the 3-week DOCA-salt-treated groups (0.25 +/- 0.14 vs 1.03 +/- 0.10 ml/min). These data suggest that the renal nerves contribute to the early established phase of DOCA-salt hypertension by shifting the arterial pressure-renal sodium excretion curve to the right. With time, the renal nerves play a diminishing role in the maintenance of established DOCA-salt hypertension in the rat, while other renal factors, including decreased glomerular filtration rate and probable fixed renal vascular changes, play an increasingly important role.

Animals↗
PubMedDate not supplied

Kidney function and sodium handling in the pregnant spontaneously hypertensive rat.

Effects of gestation on volume homeostasis and renal function were studied in awake spontaneously hypertensive rats (SHR). Systolic blood pressure was similar to that of virgin littermates during most of SHR pregnancy but decreased near term (p less than 0.005). Plasma renin activity was lower in SHR than in age-matched Wistar-Kyoto (WKY) rats (p less than 0.001), but values were similar in gravid and nonpregnant animals from each strain. Renal renin content and lipid volume fractions of papillary interstitial granules were significantly greater in pregnant animal of each strain and those of the gravid WKY were also greater than both pregnant and virgin SHR. Saralasin had no effect on mean arterial pressure in gravid and virgin rats from either group. Plasma volume increased significantly near term in animals of both strains. Kidney weight, glomerular filtration rate (GFR), and renal blood flow were lower in SHR compared to WKY, and the hypertensive rats failed to demonstrate an increase in GFR during gestation, unlike the WKY. All SHR and pregnant WKY excreted infused sodium better than the virgin WKY. Also, regular Wistar animals excreted a salt load better than the virgin WKY. Finally, uterine blood flow, pup number and conceptus weight were similar in SHR and WKY. We conclude that pregnancy induces a decrease in blood pressure in SHR, and that angiotensin II does not seem to play an important role in maintaining blood pressure during gestation in either SHR or WKY. Despite a lower GFR and its failure to increase during pregnancy, renal sodium handling is not impaired in the SHR. The virgin WKY has a decreased ability to excrete sodium which is ameliorated during gestation.

Animals↗
PubMedDate not supplied

Attenuation of the development of spontaneous hypertension in rats by chronic central administration of captopril.

Captopril infused into the lateral ventricle (ICV) of adult spontaneously hypertensive rats (SHR) decreases blood pressure. The current study was designed to explore the effects of brain converting-enzyme inhibition in young animals before the development of established hypertension and to characterize changes induced by captopril in a variety of pressor systems that might be responsible for the development of hypertension in this strain. Captopril (1.25 micrograms/0.5 microliter/hr) was infused into male SHR starting at 7 weeks of age. Four weeks later systolic blood pressure was only 157 +/- 3.3 compared to 181 +/- 3.9 mm Hg in vehicle-infused controls, and the pressor effect of ICV-injected angiotensin I was attenuated by 50%. When the same dose of captopril was infused intravenously, hypertension progressed as in vehicle-treated rats. Serum angiotensin-converting enzyme activity (SACE) and plasma arginine vasopressin (AVP) concentration were significantly higher (p less than 0.001 and 0.05, respectively), in the ICV captopril group than in the ICV vehicle group, while plasma aldosterone concentration and renin activity, fluid intake, urine volume, and urinary sodium excretion were similar in the two groups. Peripheral sympathetic nervous system activity assessed in the resting state was not altered by captopril treatment. In addition, AVP content of the telencephalon, diencephalon, mesencephalon, and pons medulla were not altered by ICV captopril. Renin activity was elevated in the telencephalon of ICV captopril-treated animals but unaltered in the other brain regions examined. These data demonstrate that ICV administration of captopril attenuates the development of hypertension in young SHR by mechanisms apparently independent of altered fluid and sodium balance and the sympathoadrenal system. The effect on blood pressure occurs in the absence of changes in renin activity or AVP content of plasma or those brain regions most often associated with blood pressure control.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Altered vascular reactivity and baroreflex sensitivity induced by chronic central administration of captopril in the spontaneously hypertensive rat.

Previous studies from our laboratory have shown that chronic intracerebroventricular administration of captopril attenuates the development of hypertension in the spontaneously hypertensive rat of the Okamoto strain (SHR) without altering sodium and water balance, plasma renin, or sympathoadrenal activities. To determine whether the depressor effect of intracerebroventricular captopril was associated with an alteration in peripheral vascular reactivity and/or baroreflex sensitivity, vascular reactivity to phenylephrine and vasopressin was assessed in renal, mesenteric, and hindquarter vascular beds using pulsed Doppler flow probes. Captopril was infused into the jugular vein or lateral ventricle of male SHR and Wistar-Kyoto (WKY) rats for 4 weeks (osmotic mini pump, 1.25 micrograms/0.5 microliter/hr). Control SHR or WKY received intracerebroventricular infusions of vehicle. Four weeks of captopril decreased arterial pressure in both SHR and WKY. In response to phenylephrine and vasopressin, SHR and WKY treated with intracerebroventricular captopril showed significantly attenuated increases in arterial pressure and vascular resistance in comparison to either vehicle-treated rats or rats receiving intravenous captopril. Reflex decreases in heart rate in response to phenylephrine were also greater in SHR and WKY treated with intracerebroventricular captopril than in the other rat groups. Neither vascular reactivity nor baroreflex sensitivity was altered in rats treated with intravenous captopril. We conclude that the depressor effect of captopril involves a blunting of vascular reactivity to vasoconstrictors and a potentiation of the baroreflex.

Animals↗
PubMedDate not supplied

Myocardial cell hypertrophy or hyperplasia.

Growth of the vertebrate heart during embryonic and fetal life is characterized by hyperplasia of myocardial cells; these cells increase in number to a value characteristic for each species. Shortly after birth myocardial cells lose the capability of dividing, and further growth of the heart is due to myocardial cell hypertrophy and nonmuscle cell hyperplasia. This process, which is referred to as hypertrophic growth, results in a 30- to 40-fold increase in volume of individual myocardial cells during normal postnatal growth and maturation. The transition from hyperplastic to hypertrophic growth is related to formation of binucleated myocardial cells as a result of karyokinesis without cytokinesis. The molecular mechanism of this transition is uncertain. The response of the heart to increased metabolic demands or to an increased workload depends on the age of the animal at the time the stress is imposed. Increased myocardial workloads due to systemic hypertension, chronic hypoxia, or carbon monoxide exposure in fetal or early neonatal life lead to cardiac enlargement by causing an increased rate of hyperplasia of myocardial cells or continuation of hyperplasia beyond the normal period of hyperplastic growth. In contrast, imposition of increased loads on the hearts of older animals results in cardiac hypertrophy due to enlargement of myocardial cells and hyperplasia of nonmuscular components. In addition to cellular enlargement, structural remodeling of the myocardial cells, including alterations in the relative proportions of cellular organelles and in the ultrastructure of individual organelles, occurs during the development of hypertrophy in the adult heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMedDate not supplied

High blood pressure in women.

There is a sexual dimorphism in blood pressure of humans and experimental animals: males tend to have higher blood pressure than females with functional ovaries, while ovariectomy or menopause tends to abolish the sexual dimorphism and cause females to develop a "male" pattern of blood pressure. Hypertensive male laboratory animals tend to have NaCl-sensitive blood pressure, while females are NaCl resistant unless their ovaries are removed, in which case NaCl sensitivity appears. The hormonal basis of NaCl sensitivity of blood pressure and of the sexual dimorphism of hypertension remains to be defined. Synthetic estrogens and progestins, as found in oral contraceptives, tend to elevate blood pressure, while naturally occurring estrogens lower it, or have no effect. Hypertension increases cardiovascular risk in women, as well as men, although the benefits of antihypertensive treatment have been more difficult to demonstrate in women. In the population of the United States, women are more aware of their hypertension, more likely to be treated medically, and more likely to have their blood pressure controlled.

Adult↗