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Biomedical subjects

S Oparil

Publications and source records attributed to S Oparil.

At least 127 records · Page 7Linked to original sources
PubMed1995

Racial differences in the pathogenesis of hypertension.

Hypertension occurs at an earlier age, is more prevalent, and is more often complicated by target organ damage in African-Americans than whites. Reasons for this increased severity of hypertension in African-Americans remain obscure. Based on studies recently completed in their laboratory, the authors propose that greater sympathetic reactivity to stress and a greater prevalence of NaCl sensitivity contribute to the earlier development of hypertension in African-Americans. Using microneurography to record muscle sympathetic nervous system activity, it was found that normotensive blacks manifest greater increases in sympathetic activity to cold stress than normotensive whites. If true of other types of stressors, greater sympathetic reactivity would predispose blacks to the development of hypertension. Using a telemetry-based monitoring system, the authors recently reported that both spontaneously hypertensive rats and normotensive Wistar-Kyoto rats manifest acute sensitivity to high dietary NaCl ingestion, but that the Wistar-Kyoto rats are able to compensate, thereby avoiding sustained increases in blood pressure. Based on these animal studies, it is proposed that elevated nocturnal pressures observed in blacks by other investigators may reflect the greater prevalence of NaCl sensitivity in the black population. As in animal models of NaCl-sensitive hypertension, blacks may retain ingested NaCl, resulting in sustained increases in blood pressure.

Animals↗
PubMed1995

Hypertension in postmenopausal women: pathophysiology and management.

Hypertension, particularly systolic hypertension, afflicts over 50% of postmenopausal women and is an important risk factor for cardiovascular disease in this group. Hormone replacement therapy with estrogen or an estrogen/progestin combination does not alter blood pressure but has beneficial effects on other cardiovascular risk factors, so should be considered in all postmenopausal women unless contraindicated.

Estrogen Replacement Therapy↗
PubMed1995

Increased ACE and chymase-like activity in cardiac tissue of dogs with chronic mitral regurgitation.

The current study was designed to test the hypothesis that intracardiac angiotensin-converting enzyme (ACE) activity, chymase-like activity, and angiotensin (ANG) peptide levels are increased and are positively related to wall stress estimates in response to the chronic low pressure volume overload of mitral regurgitation produced by percutaneous chordal rupture in the dog. Chronic mitral regurgitation (MR) resulted in an increase in left ventricular (LV) end-diastolic volume [59 +/- 11 (SD) to 103 +/- 32 ml, P < 0.001], LV mass (96 +/- 17 to 114 +/- 23 g, P < 0.001), and a decrease in the LV mass-to-end-diastolic volume ratio (1.64 +/- 0.22 to 1.16 +/- 0.23 g/ml, P < 0.001) measured by magnetic resonance imaging. In vitro studies of heart tissue extracts demonstrated that the majority of ANG II-forming activity was from chymase-like activity rather than from ACE activity in five normal (83.5 +/- 7.5 vs. 6.04 +/- 5.2%) and seven MR hearts (86 +/- 3.9 vs. 2.6 +/- 1.7%). ACE activity (1.22 +/- 0.22 vs. 3.55 +/- 0.62 mU/g, P < 0.05) and chymase-like activity (9.42 +/- 4.64 vs. 20.60 +/- 8.41 nmol.g-1.min-1, P < 0.05) were increased in MR compared with normal hearts. ACE activity correlated with the LV mass-to-volume ratio (r = -0.93, P < 0.001) and LV diastolic wall stress ( r = 0.71, P < 0.05); however, chymase-like activity did not correlate with any hemodynamic parameter. ANG II levels were significantly higher in the midwall of the left ventricle in MR hearts than in normal controls (85 +/- 39 vs. 27 +/- 16 pg/g, P < 0.01). Our results demonstrate a positive correlation between LV diastolic wall stress and increased ACE activity with increased ANG II stores, suggesting that mechanical wall stress activated intracardiac ACE. Although chymase accounted for most ANG II formation in vitro in extracts of both normal and MR dog hearts, the significance of this enzyme in vivo remains unclear.

Angiotensin II↗
PubMed1995

Endothelin-A receptor antagonist prevents acute hypoxia-induced pulmonary hypertension in the rat.

Exposure to hypoxia is associated with increased pulmonary artery pressure and plasma endothelin-1 (ET-1) levels and with selective enhancement in ET-1 peptide and mRNA and endothelin-A (ETA) receptor mRNA levels in rat lung. The current study tested the hypothesis that endogenous ET-1 can account for hypoxia-induced pulmonary hypertension via a paracrine effect on ETA receptors in lung. Intravenous infusion of the ETA receptor antagonist BQ-123 (D-Trp-D-Asp-Pro-D-Val-Leu) (0.4 mg/microliters at 1 microliter/h) into Sprague-Dawley rats beginning 4 h before and for 90 min during normobaric hypoxia (10% O2) markedly attenuated the hypoxic response: mean pulmonary artery pressure increased from 17.2 +/- 0.7 to 29.0 +/- 1.2 mmHg in saline control rats but did not increase from baseline in BQ-123-treated rats. BQ-123 did not alter systemic arterial pressure, heart rate, or plasma endothelin-1 levels. These findings suggest that ET-1 synthesized in lung in response to hypoxia acts locally on ETA receptors to cause pulmonary hypertension.

Acute Disease↗
PubMed1995

Selective downregulation of ANP-clearance-receptor gene expression in lung of rats adapted to hypoxia.

To test the hypothesis that expression of atrial natriuretic peptide (ANP)-receptor genes is modified to provide a compensatory mechanism against hypoxic pulmonary hypertension, steady state mRNA levels for the ANP-A receptor (or guanylate cyclase-A; ANPAR), ANP-B receptor (or guanylate cyclase-B; ANPBR), and ANP-clearance receptor (ANPCR) were quantitated by Northern blot and slot-blot analysis in lung, kidney, spleen, and liver of hypoxia-adapted rats and air controls. Exposure of rats to short-term (48 h) and chronic (4 wk) hypoxia (10% O2, 1 atm) did not affect lung ANPAR-mRNA levels. Lung ANPBR-mRNA levels were unchanged by short-term hypoxia but selectively increased (approximately twofold) by chronic hypoxia. ANPCR-mRNA levels were selectively and significantly downregulated by 48-h and 4-wk hypoxia in lung but were unchanged or upregulated in other tissues. Lung ANPCR gene transcription, assessed by nuclear-runoff analysis, was decreased by hypoxia. These data support the conclusion that altered pulmonary ANP-receptor gene expression modulates the development of hypoxic pulmonary hypertension.

Adaptation, Physiological↗
PubMed1995

ETA-receptor antagonist prevents and reverses chronic hypoxia-induced pulmonary hypertension in rat.

The selective endothelin-A (ETA)-receptor antagonist BQ-123 has been shown to prevent chronic hypoxia-induced pulmonary hypertension in the rat. Therefore in the current study we utilized BQ-123 to test the hypothesis that blockade of the ETA receptor can reverse as well as prevent the increase in mean pulmonary artery pressure, right ventricle-to-left ventricle plus septum ratio, and percent wall thickness in small (50-100 microns) pulmonary arteries observed in male Sprague-Dawley rats exposed to normobaric hypoxia (10% O2, 2 wk). Infusion of BQ-123 (0.4 mg.0.5 microliter-1.h-1 for 2 wk in 10% O2) begun after 2 wk of hypoxia significantly reversed the established pulmonary hypertension and prevented further progression of right ventricular hypertrophy during the third and fourth week of hypoxia. BQ-123 infusion instituted before exposure to hypoxia completely prevented the hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular remodeling. These findings suggest that, in the lung, hypoxia induced an increase synthesis of endothelin-1, which acts locally on ETA receptors to cause pulmonary hypertension, right heart hypertrophy, and pulmonary vascular remodeling, while ETA-receptor blockade can both prevent and reverse these processes.

Animals↗
PubMed1995

Endothelin-receptor antagonist bosentan prevents and reverses hypoxic pulmonary hypertension in rats.

The current study examined the effects of bosentan, an orally active antagonist of endothelin-A and -B receptors, on the development and maintenance of hypoxia (10% O2)-induced pulmonary hypertension and vascular remodeling in the rat. Pretreatment with bosentan (100 mg.kg-1.day-1, 1 gavage/day for 2 days) completely blocked the pulmonary vasoconstrictor response to acute hypoxia. Chronic bosentan treatment (100 mg.kg-1.day-1 po in the food) instituted 48 h before hypoxic exposure prevented the subsequent development of pulmonary hypertension, attenuated the associated right heart hypertrophy, and prevented the remodeling of small (50-100 microns) pulmonary arteries without altering systemic arterial pressure. Institution of bosentan treatment (for 4 wk) after 2 wk of hypoxia produced a significant reversal of established hypoxia-induced pulmonary hypertension (from 36 +/- 1 to 25 +/- 1 mmHg), right heart hypertrophy, and pulmonary vascular remodeling despite continuing hypoxic exposure. These findings support the hypothesis that endogenous endothelin-1 plays a major role in hypoxic pulmonary vasoconstriction and/or hypertension, right heart hypertrophy, and pulmonary vascular remodeling and suggest that endothelin-receptor blockade may be useful in the treatment of hypoxic pulmonary hypertension humans.

Animals↗
PubMed1995

Acute hypertension increases norepinephrine release in the anterior hypothalamic area.

Neurons in the anterior hypothalamic area play an important role in NaCl-sensitive hypertension in spontaneously hypertensive rats, and previous studies have suggested that baroreceptor feedback modifies the activity of these neurons. To test the hypothesis that the release of norepinephrine in the anterior hypothalamic area is modified by arterial baroreceptor reflex feedback and that this reflex release is disturbed in spontaneously hypertensive rats on a high NaCl diet, we used the push-pull technique to measure the release of the norepinephrine metabolite 3-methoxy-4-hydroxy-phenylglycol in the anterior hypothalamic area. Seven-week-old male spontaneously hypertensive and normotensive Wistar-Kyoto rats were placed on a high (8%) or a basal (1%) NaCl diet for 2 weeks. The high NaCl diet elevated mean arterial pressure and greatly reduced basal norepinephrine metabolite levels in the anterior hypothalamic area of the spontaneously hypertensive (but not the control) rats (305 +/- 32 pg/10 min in the rats consuming 1% NaCl and 93 +/- 9 pg/10 min in the rats consuming 8% NaCl). An infusion of tramazoline (an imidizoline that causes long-lasting hypertension) that increased arterial pressure by 25 mm Hg elevated anterior hypothalamic area norepinephrine metabolite concentrations significantly more in the spontaneously hypertensive rats on the 1% NaCl diet (to 392 +/- 46 pg/10 min) than in those on the 8% NaCl diet (to 113 +/- 18 pg/10 min). In contrast, in Wistar-Kyoto rats the tramazoline-induced increase in arterial pressure elevated anterior hypothalamic area norepinephrine metabolite concentrations slightly more in rats on the 8% NaCl diet than in those on the 1% NaCl diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

Gender and dietary NaCl in spontaneously hypertensive and Wistar-Kyoto rats.

We recently reported that high dietary NaCl exposure significantly increases both daytime and nighttime mean arterial pressure in male spontaneously hypertensive rats (SHR) but only nighttime values in male normotensive Wistar-Kyoto rats (WKY). In the present study we used a telemetry monitoring system to evaluate the effects of high dietary NaCl exposure on diurnal variation of mean arterial pressure and heart rate in male and female SHR and WKY. After implantation of a radio-frequency transducer, rats were fed either high (8%) or basal (1%) NaCl diets for 2 weeks. High dietary NaCl ingestion significantly increased both daytime and nighttime mean arterial pressure in male SHR compared with males receiving a basal NaCl diet, resulting in greater 24-hour values (163 +/- versus 154 +/- 1 mm Hg, high versus basal NaCl diet; P < .05). High dietary NaCl ingestion significantly increased only nighttime blood pressure in male WKY, with no significant effect on 24-hour mean arterial pressure (102 +/- 2 versus 101 +/- 3 mm Hg, high versus basal). High dietary NaCl exposure did not affect daytime or nighttime mean arterial pressure in female SHR (24-hour mean arterial pressure, 144 +/- 2 versus 141 +/- 2 mm Hg, high versus basal NaCl diet). Twenty-four-hour mean arterial pressure tended to be lower in female WKY receiving a high NaCl diet than females ingesting a basal diet (101 +/- 3 versus 106 +/- 1 mm Hg), but the difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effects of dietary salt on angiotensin peptides in kidney.

This study used a novel simple method for the extraction, separation, identification, and quantitation of angiotensin-like immunoactivity from tissue to examine the effects of altering dietary NaCl intake on intrarenal angiotensin I, II, and III levels in salt-sensitive, spontaneously hypertensive rats, salt-resistant Wistar-Kyoto rats, and Sprague-Dawley rats. Seven-week-old male spontaneously hypertensive rats, Wistar-Kyoto rats, and Sprague-Dawley rats were assigned randomly to a diet containing either 8% (high) or 1% (basal) salt and were maintained on these diets for 3 wk. Rats were then decapitated without prior anesthesia, and kidneys were rapidly (< 30 s) removed, snap frozen in liquid nitrogen, and stored at -80 degrees C. Frozen tissue was extracted in 2 M acetic acid and then subjected to solid-phase extraction with the cation exchange resin AG 50W X4. Angiotensin peptides were separated by reversed-phase high-performance liquid chromatography on a phenyl silica gel column with an eluent consisting of 20% acetonitrile in 0.1 M ammonium phosphate buffer, pH 4.9, and quantitated by radioimmunoassay. The elution of standard peptides under isocratic conditions revealed clear resolution of angiotensin I, II, and III and the (1-7) and (3-8) peptides. Recoveries of both labeled and unlabeled angiotensin peptide standards from the extraction step were > 90%. Renal angiotensin II stores were significantly higher in spontaneously hypertensive rats than in Wistar-Kyoto or Sprague-Dawley rats, independent of diet. Renal angiotensin II and III were further suppressed during dietary salt supplementation in both salt-resistant strains but not in the spontaneously hypertensive rat. These findings are consistent with an enhanced (compared with Wistar-Kyoto and Sprague-Dawley rats) role for angiotensin II in the kidney of the salt-sensitive, spontaneously hypertensive rat, particularly under conditions of dietary salt supplementation.

Angiotensin I↗
PubMed1994

Sodium-proton (Na+/H+) exchange inhibition increases blood pressure in spontaneously hypertensive rat.

The current study was designed to determine the role of sodium-proton (Na+/H+) exchange in blood pressure regulation in sodium chloride (NaCl)-sensitive and NaCl-resistant spontaneously hypertensive rats and control Wistar-Kyoto rats (WKY) using 5-(N,N-hexamethylene)amiloride (HMA), a potent and selective inhibitor of Na+/H+ exchange. The response of mean arterial pressure to intravenous infusion of HMA was examined in conscious, unrestrained male rats maintained on normal (1%) or high (8%) NaCl diets for 3 weeks beginning at age 7 weeks. The HMA significantly increased mean arterial pressure in NaCl-sensitive spontaneously hypertensive rats and NaCl-resistant spontaneously hypertensive rats that were fed 1% NaCl, but not in WKY rats that were fed 1% NaCl; the 8% NaCl diet enhanced this pressor response in all 3 strains. The pressor response was accompanied by significant increases in plasma norepinephrine levels in NaCl-sensitive spontaneously hypertensive rats on both diets, but not in NaCl-resistant spontaneously hypertensive rats or WKY rats on either diet. There were no differences in steady-state levels (30-60 nM) of plasma HMA between diet groups in any strain. Therefore, administration of HMA in a dose at which it is highly selective for the Na+/H+ exchanger (Ki = 160 nM) caused a systemic pressor response in spontaneously hypertensive rats that was enhanced by dietary NaCl supplementation. With these data, it is suggested that inhibition of Na+/H+ exchange in vivo has a pressor effect greater in spontaneously hypertensive rats than in WKY rats and is further enhanced by NaCl supplementation.

Amiloride↗
PubMed1994

Increased endothelin receptor gene expression in hypoxic rat lung.

Our previous studies demonstrated that exposure to hypoxia increases pulmonary artery pressure and plasma endothelin-1 (ET-1) levels and selectively enhances ET-1 gene expression in rat lung. The current study examined the effects of hypoxia (48 h, 10% O2, 1 atm) on ET-1 and endothelin A (ETA) and ETB receptor steady-state mRNA levels in lung, heart, pulmonary artery, thoracic aorta, superior vena cava, kidney, spleen, and liver of the rat. In lung, hypoxic exposure was associated with significant increases in ET-1 mRNA (4.1-fold), ET-1 peptide (1.5-fold) and ETA mRNA (2.3-fold) levels; ETB mRNA levels were unchanged. ET-1 mRNA was increased in response to hypoxia in pulmonary artery but not in aorta; both ETA and ETB receptor steady-state mRNA levels were increased in thoracic aorta, left atrium, and right ventricle, and tended to be increased in right atrium of hypoxia-exposed rats, compared with air controls. ETB but not ETA receptor steady-state mRNA levels were increased in pulmonary artery of hypoxia-exposed rats. No change in expression of either ET receptor steady-state mRNA levels was seen in organs perfused by the systemic vascular bed. In no case were ET receptor mRNA levels in hypoxic rats reduced below air control levels, despite elevations in local and/or circulating ET-1. These findings are consistent with a role for ET-1, acting through ETA receptors, in the pathogenesis of hypoxia-induced pulmonary hypertension.

Animals↗
PubMed1994

Enhanced endothelin-1 and endothelin receptor gene expression in chronic hypoxia.

To test the hypothesis that endothelin (ET)-1 synthesis and ET receptor levels are increased selectively in the lung of rats with chronic hypoxic pulmonary hypertension, the current study examined the effects of exposure to chronic hypoxia (10% O2, 1 atm, 4 wk) on pulmonary arterial pressure, ET-1 levels in plasma and lung, and ET-1 and ETA and ETB receptor mRNA levels in lung, heart, pulmonary artery, aorta, kidney, spleen, and liver. Hypoxic exposure was associated with increases in pulmonary arterial pressure, plasma ET-1 levels, ET-1 mRNA in lung and pulmonary artery, and ET-1 stores and ETA and ETB receptor mRNA levels in lung. In thoracic aorta and the four heart chambers, ETA and ETB receptor mRNA levels were increased, but ET-1 mRNA levels were unchanged from air control levels. No change in ET-1 or ET receptor mRNA levels was seen in organs perfused by the systemic vascular bed, except in liver, where ETA receptor mRNA levels were decreased. The findings of concomitant increases in gene transcript levels for ET-1 and the ETA and ETB receptors in lung, but not in the great vessels or any other organ examined, are consistent with the hypothesis that increased ET-1 synthesis in the lung contributes to pulmonary vascular remodeling and the maintenance of chronic hypoxic pulmonary hypertension.

Animals↗
PubMed1994

Mithramycin inhibits myointimal proliferation after balloon injury of the rat carotid artery in vivo.

BACKGROUND: Smooth muscle proliferation and extracellular matrix formation in the subintimal region of blood vessels that have been subjected to intimal injury are responsible for restenosis following balloon angioplasty of the coronary arteries and for accelerated atherosclerosis in a variety of other pathophysiological states. The immediate early-response gene c-myc is overexpressed in proliferating vascular smooth muscle cells in vitro, and c-myc antisense oligomers have been shown to reduce c-myc expression and to inhibit proliferation of vascular smooth muscle cells in culture. Mithramycin is a commercially available G-C-specific DNA binding drug that selectively inhibits transcription of genes, such as c-myc, that have G-C-rich promoter sequences. This study tested the hypothesis that mithramycin inhibits transcription of the c-myc proto-oncogene and prevents myointimal proliferation after balloon injury of the rat carotid artery in vivo. METHODS AND RESULTS: Ten-week-old male Sprague-Dawley rats received mithramycin (150 micrograms/kg IP) or distilled H2O 1 hour before and 1 hour after balloon injury of the right common carotid artery. After 2 weeks, the rats were killed by overdose of pentobarbital, and the injured right and uninjured control left arteries were pressure-fixed and subjected to morphological analysis for evaluation of the degree of myointimal thickening. Separate groups of rats were killed at 2 and 6 hours after vascular injury, and total RNA from injured and control vessels of mithramycin- and vehicle-treated rats was subjected to Northern analysis for assessment of steady-state c-myc mRNA levels. The areas of neointima and the ratios of neointimal to medial area were significantly less in mithramycin-treated than in control rats (0.6 +/- 0.1 versus 1.2 +/- 0.1 mm2, P < .01 and 95 +/- 16% versus 190 +/- 14%, P < .01). Lumen size was significantly greater in mithramycin-treated than in control rats (1.5 +/- 0.1 versus 0.8 +/- 0.1 mm2, P < .01). Steady-state c-myc mRNA levels were increased 10-fold and 2-fold (compared with undamaged carotid arteries) at 2 and 6 hours after balloon injury, respectively; mithramycin treatment reduced c-myc mRNA levels at 2 and 6 hours by 66% and 53%, respectively. CONCLUSIONS: These results support the hypothesis that systemic administration of mithramycin immediately (1 hour before and after intervention effectively inhibits transcription of the c-myc proto-oncogene and prevents myointimal proliferation after balloon injury of the rat carotid artery in vivo. Because mithramycin has been shown to be well tolerated by humans and to effectively inhibit transcription of c-myc in proliferating human cells, this agent may be useful in the prevention of coronary restenosis.

Angioplasty, Balloon↗
PubMed1994

Diurnal blood pressure variation and dietary salt in spontaneously hypertensive rats.

We have previously reported that high dietary salt exposure significantly increases daytime mean arterial pressure in spontaneously hypertensive rats (SHR) but not in normotensive Wistar-Kyoto (WKY) controls. In the present study, we used a telemetry monitoring system to evaluate the effects of high dietary salt exposure on diurnal variation of mean arterial pressure and heart rate in SHR and WKY rats. After implantation of a radio frequency transducer, SHR and WKY rats were maintained on either high (8%) or basal (1%) salt diets. Hemodynamic values were then analyzed for diurnal variation with the use of a nonlinear data-fitting program. After 2 weeks of dietary exposure, high salt-fed SHR had significantly greater 24-hour mean arterial pressure (156 +/- 3 mmHg) than SHR receiving basal (135 +/- 2 mmHg) and WKY rats receiving high (100 +/- 2 mmHg) or basal (100 +/- 1 mmHg) salt diets. Rhythm analysis indicated significant increases in both daytime and nighttime mean arterial pressure during high salt exposure in SHR. In WKY rats, high salt exposure increased nighttime but not daytime mean arterial pressure, with no net effect on 24-hour mean arterial pressure. High dietary salt exposure significantly decreased heart rate in both SHR and WKY rats, and it did not significantly alter the pattern of diurnal blood pressure or heart rate variation. These results indicate that WKY rats manifest an acute sensitivity to salt ingestion but have compensatory mechanisms sufficient to prevent sustained increases in mean arterial pressure; such mechanisms are lacking in SHR.

Animals↗
PubMed1994

The role of atrial natriuretic peptide and endothelin in hypoxia induced pulmonary hypertension.

The goal of our studies is to elucidate the role of atrial natrluretic peptide (ANP) and endothelin-1 (ET-1) and their receptor mechanisms in hypoxia-induced pulmonary hypertension and the control of pulmonary artery pressure in patients with pulmonary hypertension. Our experimental model is the male Sprague-Dawley rat subjected to normobaric hypoxia (10% O2, 1 atm) x 4 weeks or less. Our hypothesis is that ET-1 and ANP gene expression are enhanced by exposure to hypoxia and that the ET-1 and ANP so generated have causal and protective, respectively, effects on the development of hypoxia-induced pulmonary hypertension. Results from our studies demonstrated that ANP gene expression and ANP secretion in the heart, and the sensitivity to both endogenous and exogenous ANP in the pulmonary vasculature of hypoxia adapted rats are enhanced during hypoxic exposure. These data defined a role for ANP as a modulator hormone that protects against the development of acute hypoxic pulmonary vasoconstriction and chronic hypoxic pulmonary hypertension. Our studies also demonstrated that ET-1 and endothelin-A receptor (ET-AR) gene expression were selectively enhanced in the pulmonary vasculature by exposure to hypoxia, and that the ET-1 so generated is an important mediator in acute and chronic hypoxia-induced pulmonary hypertension. These results suggest that the intrapulmonary ET-1, acting on ET-AR receptors in the pulmonary vasculature mediates the hypoxia-induced pulmonary vasoconstriction and hypertension. In addition, our recent experiments have demonstrated that administration of BQ-123, a selective ET-AR antagonist, abolished the pulmonary vasoconstrictor response to acute (0-90 min) and chronic (2 weeks) hypoxia, further suggesting that ET-1 plays an important role in the pathogenesis of hypoxia-induced pulmonary hypertension in the rat. Results from our studies also indicate that selective ANP analogs and ET-AR antagonists may be clinically useful for the treatment of pulmonary hypertension.

Animals↗