Renal dopamine DA1 receptor coupling with G(S) and G(q/11) proteins in spontaneously hypertensive rats

1997 ◽  
Vol 272 (3) ◽  
pp. F339-F346 ◽  
Author(s):  
T. Hussain ◽  
M. F. Lokhandwala
Keyword(s):  
G Protein ◽  
Spontaneously Hypertensive Rats ◽  
Sch 23390 ◽  
Hypertensive Rats ◽  
G Protein Coupling ◽  
Spontaneously Hypertensive ◽  
Protein Coupling ◽  
Basolateral Membranes ◽  
Wky Rats ◽  
Stimulation Of

The dopamine DA1 receptor transduces its signal via adenylyl cyclase and phospholipase C in the renal proximal tubule, which has been suggested to be defective at the level of receptor-G protein coupling in spontaneously hypertensive rats (SHR). We prepared basolateral membranes from Wistar-Kyoto (WKY) rats and SHR to determine the coupling of DA1 receptor with G proteins, especially G(q/11). Fenoldopam, a DA1-receptor agonist, produced a time- and concentration-dependent stimulation in 35S-labeled guanosine 5'-O-(3-thiotriphosphate) ([35S]GTPgammaS) binding in WKY rats. Fenoldopam-induced (10 microM) stimulation was significantly inhibited by a DA1-receptor antagonist, Sch-23390. Specific antibodies against COOH terminals of G(S)alpha and G(q/11)alpha produced 50-60% and 40-50% inhibition, respectively, in fenoldopam stimulation of [35S]GTPgammaS binding. Western analysis of basolateral membranes with these antibodies revealed the presence of G(S)alpha (45 kDa) and G(q/11)alpha (42 kDa). Fenoldopam stimulation of [35S]GTPgammaS binding was significantly attenuated in SHR compared with WKY rats. Parathyroid hormone stimulation of [35S]GTPgammaS binding was similar in SHR and WKY rats, whereas stimulation by phenylephrine was significantly reduced in SHR. Densitometric quantification of 42-kDa band showed a reduced amount in SHR, whereas the density of 45-kDa band was not significantly different compared with WKY rats. We provide the direct evidence showing the coupling of DA1 receptor with G(q/11)alpha and G(S)alpha and propose that, in addition to a defect in the receptor-G protein coupling, a reduced amount of G(q/11)alpha observed in the hypertensive animals may also contribute to the diminished dopamine-induced inhibition of Na+-K+-adenosinetriphosphatase in SHR.

Defective nitric oxide production impairs angiotensin II-induced Na-K-ATPase regulation in spontaneously hypertensive rats

2012 ◽  
Vol 302 (1) ◽  
pp. F47-F51 ◽  
Author(s):  
Apurva A. Javkhedkar ◽  
Mustafa F. Lokhandwala ◽  
Anees Ahmed Banday
Keyword(s):  
Nitric Oxide ◽  
Spontaneously Hypertensive Rats ◽  
Proximal Tubules ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
High Concentration ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Proximal Tubular ◽  
Stimulation Of

Angiotensin (ANG) II via ANG II type 1 receptors (AT1R) activates renal sodium transporters including Na-K-ATPase and regulates sodium homeostasis and blood pressure. It is reported that at a high concentration, ANG II either inhibits or fails to stimulate Na-K-ATPase. However, the mechanisms for these phenomena are not clear. Here, we identified the signaling molecules involved in regulation of renal proximal tubular Na-K-ATPase at high ANG II concentrations. Proximal tubules from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were incubated with low concentrations of ANG II (pM), which activated Na-K-ATPase in both the groups; however, the stimulation was more robust in SHR. A high concentration of ANG II (μM) failed to stimulate Na-K-ATPase in WKY rats. However, in SHR ANG II (μM) continued to stimulate Na-K-ATPase, which was sensitive to the AT1R antagonist candesartan. In the presence of NG-nitro-l-arginine methyl ester (l-NAME), a nitric oxide (NO) synthase (NOS) inhibitor, ANG II (μM) caused stimulation of Na-K-ATPase in proximal tubules of WKY rats while having no further stimulatory effect in SHR. ANG II (μM), via AT1R, increased proximal tubular NO levels in WKY rats but not in SHR. In SHR, NOS was uncoupled as incubation of proximal tubules with ANG II and l-arginine, a NOS substrate, caused superoxide generation only in SHR and not in WKY rats. The superoxide production in SHR was sensitive to l-NAME. There was exaggerated proximal tubular AT1R-G protein coupling and NAD(P)H oxidase activation in response to ANG II (μM) in proximal tubules of SHR compared with WKY rats. In SHR, inhibition of NADPH oxidase restored NOS coupling and ANG II-induced NO accumulation. In conclusion, at a high concentration ANG II (μM) activates renal NO signaling, which prevents stimulation of Na-K-ATPase in WKY rats. However, in SHR ANG II (μM) overstimulates NADPH oxidase, which impairs the NO system and leads to continued Na-K-ATPase activation.

Stimulation of brain cannabinoid CB 1 receptors can ameliorate hypertension in spontaneously hypertensive rats

2020 ◽  
Vol 47 (7) ◽  
pp. 1254-1262
Author(s):  
Takahiro Shimizu ◽  
Masaki Yamamoto ◽  
Suo Zou ◽  
Shogo Shimizu ◽  
Youichirou Higashi ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Stimulation Of

Abstract 11003: Hypothalamic Activated Microglia With Morphological Changes Accelerate Blood Pressure Elevation During the Hypertension Development Phase in Stroke-prone Spontaneously Hypertensive Rats

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ko Takesue ◽  
Takuya Kishi ◽  
Yoshitaka Hirooka
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Development Phase ◽  
Hypertensive Rats ◽  
Blood Pressure Elevation ◽  
Spontaneously Hypertensive ◽  
Activated Microglia ◽  
Wky Rats ◽  
Pressure Elevation ◽  
Hypertension Development

Introduction: A recent paradigm shift in cardiovascular pathophysiology is the impact of inflammation on hypertension. Inflammation within the paraventricular nucleus of the hypothalamus (PVN) is an important pathology of sympathetic hyperactivity, and is mainly mediated by innate immune cells, microglia. Activated microglia with alteration of their morphology produce inflammatory cytokines. Previous reports demonstrated that microglia within the PVN have activated morphology in angiotensin II-induced hypertensive rats and spontaneously hypertensive rats compared with normotensive control Sprague-Dawley rats or Wistar-Kyoto (WKY) rats. However, the role of activated microglia in the PVN in blood pressure elevation associated with sympathetic hyperactivity remains unknown. In the present study, we determined whether inhibition of microglial activation within the PVN attenuates the blood pressure elevation in genetically hypertensive rats. Methods and Results: We evaluated the activation of PVN microglia, identified by microglia specific ionized calcium-binding adaptor molecule 1 immunoreactivity, by measuring the roundness and the perimeter of microglia at 6 weeks of age, early hypertension development phase in stroke-prone spontaneously hypertensive rats (SHRSP) and compared with them in age-matched normotensive WKY rats. At 6 weeks of age, increased roundness and shortening of perimeter of microglia, indicating activated microglia, were observed in SHRSP compared with those in WKY rats. Then, we performed intracerebroventricular (ICV) administration of minocycline (5 μg/h) to deactivate microglia at 6 weeks of age for 4 weeks. ICV administration of minocycline significantly attenuated systolic blood pressure elevation in SHRSP over 4 weeks (at the end of experiments; 203.2±2.2 mm Hg vs. 215.9±2.7 mm Hg, n=8-9, P<0.05), but not in WKY rats. At 10 weeks of age, morphological analysis revealed that ICV minocycline significantly decreased the roundness and increased the perimeter of microglia, indicating deactivation of microglia, within the PVN in SHRSP. Conclusions: Hypothalamic activated microglia with morphologic changes accelerate blood pressure elevation during the hypertension development phase in SHRSP.

Vasopressin V2 receptor enhances gain of baroreflex in conscious spontaneously hypertensive rats

1999 ◽  
Vol 276 (3) ◽  
pp. R872-R879 ◽  
Author(s):  
Donella B. Sampey ◽  
Louise M. Burrell ◽  
Robert E. Widdop
Keyword(s):  
Receptor Antagonist ◽  
Spontaneously Hypertensive Rats ◽  
Pressor Response ◽  
Receptor Subtype ◽  
Hypertensive Rats ◽  
Receptor Antagonists ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Baroreflex Function ◽  
Shr And Wky Rats

The aim of the present study was to determine the receptor subtype involved in arginine vasopressin (AVP)-induced modulation of baroreflex function in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats using novel nonpeptide AVP V1- and V2-receptor antagonists. Baroreceptor heart rate (HR) reflex was investigated in both SHR and WKY rats which were intravenously administered the selective V1- and V2-receptor antagonists OPC-21268 and OPC-31260, respectively. Baroreflex function was assessed by obtaining alternate pressor and depressor responses to phenylephrine and sodium nitroprusside, respectively, to construct baroreflex curves. In both SHR and WKY rats baroreflex activity was tested before and after intravenous administration of vehicle (20% DMSO), OPC-21268 (10 mg/kg), and OPC-31260 (1 and 10 mg/kg). Vehicle did not significantly alter basal mean arterial pressure (MAP) and HR values or baroreflex function in SHR or WKY rats. The V1-receptor antagonist had no significant effect on resting MAP or HR values or on baroreflex parameters in both groups of rats, although this dose was shown to significantly inhibit the pressor response to AVP (5 ng iv; ANOVA, P < 0.05). In SHR but not WKY rats the V2-receptor antagonist significantly attenuated the gain (or slope) of the baroreflex curve (to 73 ± 3 and 79 ± 7% of control for 1 and 10 mg/kg, respectively), although AVP-induced pressor responses were also attenuated with the higher dose of the V2-receptor antagonist. These findings suggest that AVP tonically enhances baroreflex function through a V2 receptor in the SHR.

Tolerance to hypoxia of myocardium from adult and aged spontaneously hypertensive rats

1987 ◽  
Vol 252 (6) ◽  
pp. H1096-H1104 ◽  
Author(s):  
W. W. Brooks ◽  
J. S. Ingwall ◽  
C. H. Conrad ◽  
C. Holubarsch ◽  
O. H. Bing
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Energy Charge ◽  
High Energy ◽  
Left Ventricular ◽  
Adenylate Energy Charge ◽  
Papillary Muscles ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Tolerance To Hypoxia

Myocardial mechanics and high-energy phosphate content [ATP and creatine phosphate (CrP)] of isolated left ventricular papillary muscle preparations from male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were compared at 6 and 18 mo of age. In comparison with oxygenated (95% O2-5% CO2) glucose-supplied (5.5 mM) papillary muscles from hearts of WKY rats, papillary muscles from hypertrophied hearts of the 18-mo-old SHR exhibited a prolonged time to peak tension, electromechanical delay time, and an increase in resting tension measured at the apex of the length-tension curve. Adenine nucleotide (ATP and ADP) contents of oxygenated papillary muscles were not significantly different between SHR and WKY strains at 6 or 18 mo of age, but CrP content of hearts from adult WKY and SHR were higher than for aged WKY and SHR rats. For up to 30 min of hypoxia (95% N2-5% CO2), muscles from the 18-mo-old SHR and WKY rats demonstrated improved tolerance to hypoxia compared with muscles from younger animals. However, at 60 min of hypoxia the 18-mo-old SHR demonstrated lower active tension and adenylate energy charge [(1/2 ADP + ATP)/(ATP + ADP + AMP)]. At higher glucose concentrations (22 mM), both 18-mo-old WKY and SHR demonstrated improved tolerance to hypoxia; moreover, the differences between strains were no longer evident. Following reoxygenation with 5.5 mM glucose, contracture tension and CrP content recovered to near prehypoxic control levels, whereas developed tension and ATP content remained moderately depressed for all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats

2010 ◽  
Vol 299 (1) ◽  
pp. R291-R297 ◽  
Author(s):  
Cristiana A. Ogihara ◽  
Gerhardus H. M. Schoorlemmer ◽  
Adriana C. Levada ◽  
Tania C. Pithon-Curi ◽  
Rui Curi ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Spontaneously Hypertensive Rats ◽  
The Body ◽  
Swimming Exercise ◽  
Exercise Session ◽  
Hypertensive Rats ◽  
Vascular Control ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Wistar Kyoto

Inhibition of the commissural nucleus of the solitary tract (commNTS) induces a fall in sympathetic nerve activity and blood pressure in spontaneously hypertensive rats (SHR), which suggests that this subnucleus of the NTS is a source of sympathoexcitation. Exercise training reduces sympathetic activity and arterial pressure. The purpose of the present study was to investigate whether the swimming exercise can modify the regional vascular responses evoked by inhibition of the commNTS neurons in SHR and normotensive Wistar-Kyoto (WKY) rats. Exercise consisted of swimming, 1 h/day, 5 days/wk for 6 wks, with a load of 2% of the body weight. The day after the last exercise session, the rats were anesthetized with intravenous α-chloralose, tracheostomized, and artificially ventilated. The femoral artery was cannulated for mean arterial pressure (MAP) and heart rate recordings, and Doppler flow probes were placed around the lower abdominal aorta and superior mesenteric artery. Microinjection of 50 mM GABA into the commNTS caused similar reductions in MAP in swimming and sedentary SHR (−25 ± 6 and −30 ± 5 mmHg, respectively), but hindlimb vascular conductance increased twofold in exercised vs. sedentary SHR (54 ± 8 vs. 24 ± 5%). GABA into the commNTS caused smaller reductions in MAP in swimming and sedentary WKY rats (−20 ± 4 and −16 ± 2 mmHg). Hindlimb conductance increased fourfold in exercised vs. sedentary WKY rats (75 ± 2% vs. 19 ± 3%). Therefore, our data suggest that the swimming exercise induced changes in commNTS neurons, as shown by a greater enhancement of hindlimb vasodilatation in WKY vs. SHR rats in response to GABAergic inhibition of these neurons.

Alterations in renal vascular resistance and reactivity in spontaneous hypertension of rats

1980 ◽  
Vol 238 (3) ◽  
pp. H287-H293 ◽  
Author(s):  
K. H. Berecek ◽  
U. Schwertschlag ◽  
F. Gross
Keyword(s):  
Vascular Resistance ◽  
Dose Response ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Response Curves ◽  
Renal Vasculature ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Dose Response Curves ◽  
Renal Vascular

Vascular resistance and reactivity were investigated in isolated, constant flow perfused kidneys of stroke-prone spontaneously hypertensive rats (SHRSP) and age- and sex-matched normotensive Wistar-Kyoto control rats (WKY rats). Stroke-prone spontaneously hypertensive rats were studied at 4 wk, 2 mo, and 4 mo of age representing different stages of development of hypertension. Resistance in maximally vasodilated vascular beds was greater and the pressure-flow relationship was significantly shifted to the left in kidneys of SHRSP as compared to WKY rats. Responses to norepinephrine, vasopressin, serotonin, and angiotensin II were enhanced in the renal vascular bed of SHRSP. Dose-response curves were shifted to the left, had steeper slopes, decreased thresholds, and increased maximal responses. With longer duration of hypertension, resistance increased, the slopes of the dose-response curves were steeper, and maximum responses greater. The higher resistance and enhanced reactivity in the renal vasculature of SHRSP, already demonstrable in the prehypertensive stage appear to be due to primary structural and functional alterations of the resistance vessels.

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