Organ specificity of the dopamine1 receptor/adenylyl cyclase coupling defect in spontaneously hypertensive rats

1993 ◽  
Vol 264 (4) ◽  
pp. R726-R732 ◽  
Author(s):  
R. A. Felder ◽  
S. Kinoshita ◽  
K. Ohbu ◽  
M. M. Mouradian ◽  
D. R. Sibley ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Spontaneously Hypertensive Rats ◽  
Radioligand Binding ◽  
Receptor Gene ◽  
Age Groups ◽  
Organ Specificity ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Renal Dopamine

The coupling between the dopamine1 (DA1) receptor and the G protein/adenylyl cyclase (AC) enzyme complex is defective in the proximal convoluted tubule (PCT) of 20-wk-old spontaneously hypertensive rats (SHRs). Because this coupling defect could have been due to desensitization secondary to elevated renal dopamine levels in the adult animal, we studied the interaction between DA1 receptors and AC in PCT of rats as early as 3 wk of age, a time when renal dopamine levels are similar in SHRs and their normotensive controls (Wistar-Kyoto rats, WKYs). Maximum receptor density did not change with age and was similar in WKYs and SHRs in all the age groups studied (3, 8, and 20 wk). Basal-, forskolin-, and guanyl nucleotide-stimulated AC activities were also similar in WKYs and SHRs and did not change with age. However, the DA1 agonist-stimulated AC activity was greater in WKYs than in SHRs and increased with age in WKYs but not in SHRs. Moreover, the ability of a nonhydrolyzable analogue of GTP, Gpp(NH)p, to enhance DA1 agonist (SND-919-C12, 1 microM)-stimulated AC activity increased with age in WKY but not in SHRs. To determine if the defect noted in the PCT of SHRs is due to a defective D1A receptor gene, parallel studies were performed in the striatum, since this receptor is expressed predominantly in the latter tissue. In contrast to the results in PCT, radioligand binding and AC studies in striatum revealed no differences between WKYs and SHRs.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasopressin in brain of spontaneously hypertensive rats

1982 ◽  
Vol 242 (4) ◽  
pp. H496-H499 ◽  
Author(s):  
W. Rascher ◽  
R. E. Lang ◽  
T. Unger ◽  
D. Ganten ◽  
F. Gross
Keyword(s):  
Blood Pressure ◽  
Plasma Concentration ◽  
Brain Stem ◽  
Spontaneously Hypertensive Rats ◽  
Age Groups ◽  
Plasma Osmolality ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
The Brain

In stroke-prone spontaneously hypertensive rats (SHRSP) and in normotensive Wistar-Kyoto rats (WKY), arginine vasopressin (AVP) was measured by means of a radioimmunoassay in the plasma, the pituitary gland, the hypothalamus, and the brain stem. In 6- and 14-wk-old SHRSP, the plasma concentration of AVP was lower than in age-matched WKY (P less than 0.01), whereas it was elevated at 28 wk of age (P less than 0.01). In the pituitary of 6-wk-old SHRSP, AVP was higher than in WKY (P less than 0.05), but no such difference was found in older rats. In the hypothalamus and the brain stem, AVP content was reduced in all age groups of SHRSP. Plasma osmolality was diminished in 28-wk-old SHRSP only (P less than 0.01), whereas hematocrit in all age groups was higher in SHRSP than in WKY. It is concluded that the secretion of AVP and possibly its synthesis in the hypothalamus are reduced in SHRSP. Whether the reduced AVP content in the brain stem is related to the sustained elevation of blood pressure has to be studied further.

Calcium reactivity and antagonism in portal veins from spontaneously hypertensive and normotensive rats

1984 ◽  
Vol 62 (1) ◽  
pp. 146-150 ◽  
Author(s):  
A. L. Harris ◽  
V. C. Swamy ◽  
D. J. Triggle
Keyword(s):  
Inhibitory Activity ◽  
Spontaneously Hypertensive Rats ◽  
Age Groups ◽  
Induced Responses ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Activity Frequency ◽  
Blood Pressures ◽  
Portal Veins ◽  
Wistar Kyoto

Reactivities of portal veins from spontaneously hypertensive rats (SHR) and normotensive controls (Wistar Kyoto, WKY) at 5–7 and 15–17 weeks of age were compared. Systolic blood pressures were not different at 5–7 weeks but those of SHR were significantly elevated (177 ± 4 mmHg) (1 mmHg = 133.322 Pa) at 15–17 weeks. Spontaneous activity, frequency, and tension were greater in SHR for both age groups. Young SHR were more sensitive to K+ at 5–7 weeks but less sensitive at 15–17 weeks than age-matched WKY rats. Sensitivity to Ca2+ in a K+-depolarizing medium was higher in SHR than in WKY for both age groups. Maximum tension responses to K+ or Ca2+ were greater in SHR. The Ca2+ channel antagonists nifedipine, nitrendipine, and nisoldipine were potent inhibitors of both noradrenaline- and K+-induced responses but did not show differences in inhibitory activity between WKY and SHR.

Excess oxygen delivery during muscle contractions in spontaneously hypertensive rats

1995 ◽  
Vol 78 (1) ◽  
pp. 101-111 ◽  
Author(s):  
J. M. Lash ◽  
H. G. Bohlen
Keyword(s):  
Blood Flow ◽  
Oxygen Saturation ◽  
Oxygen Delivery ◽  
Spontaneously Hypertensive Rats ◽  
Muscle Contractions ◽  
Hypertensive Rats ◽  
Hemoglobin Oxygen Saturation ◽  
Spontaneously Hypertensive ◽  
Tissue Po2 ◽  
Wistar Kyoto

These experiments determined whether a deficit in oxygen supply relative to demand could account for the sustained decrease in tissue PO2 observed during contractions of the spinotrapezius muscle in spontaneously hypertensive rats (SHR). Relative changes in blood flow were determined from measurements of vessel diameter and red blood cell velocity. Venular hemoglobin oxygen saturation measurements were performed by using in vivo spectrophotometric techniques. The relative dilation [times control (xCT)] of arteriolar vessels during contractions was as large or greater in SHR than in normotensive rats (Wistar-Kyoto), as were the increases in blood flow (2 Hz, 3.50 +/- 0.69 vs. 3.00 +/- 1.05 xCT; 4 Hz, 10.20 +/- 3.06 vs. 9.00 +/- 1.48 xCT; 8 Hz, 16.40 +/- 3.95 vs. 10.70 +/- 2.48 xCT). Venular hemoglobin oxygen saturation was lower in the resting muscle of SHR than of Wistar-Kyoto rats (31.0 +/= 3.0 vs. 43.0 +/- 1.9%) but was higher in SHR after 4- and 8-Hz contractions (4 Hz, 52.0 +/- 4.8 vs. 43.0 +/- 3.6%; 8 Hz, 51.0 +/- 4.6 vs. 41.0 +/- 3.6%). Therefore, an excess in oxygen delivery occurs relative to oxygen use during muscle contractions in SHR. The previous and current results can be reconciled by considering the possibility that oxygen exchange is limited in SHR by a decrease in anatomic or perfused capillary density, arteriovenular shunting of blood, or decreased transit time of red blood cells through exchange vessels.

scholarly journals Aging Additively Influences Insulin- and Insulin-Like Growth Factor-1-Mediated Endothelial Dysfunction and Antioxidant Deficiency in Spontaneously Hypertensive Rats

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 676
Author(s):  
Kunanya Masodsai ◽  
Yi-Yuan Lin ◽  
Sih-Yin Lin ◽  
Chia-Ting Su ◽  
Shin-Da Lee ◽  
...  
Keyword(s):  
Growth Factor ◽  
Endothelial Dysfunction ◽  
Spontaneously Hypertensive Rats ◽  
No Production ◽  
Organ Bath ◽  
Insulin Like Growth Factor ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Nos Inhibitors ◽  
Wistar Kyoto

This study aimed to investigate the aging-related endothelial dysfunction mediated by insulin and insulin-like growth factor-1 (IGF-1) and antioxidant deficiency in hypertension. Male spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar–Kyoto rats (WKYs) were randomly divided into 24-week-old (younger) and 48-week-old (older) groups, respectively. The endothelial function was evaluated by the insulin- and IGF-1-mediated vasorelaxation of aortic rings via the organ bath system. Serum levels of nitric oxide (NO), malondialdehyde (MDA), catalase, and total antioxidant capacity (TAC) were examined. The insulin- and IGF-1-mediated vasorelaxation was significantly impaired in both 24- and 48-week-old SHRs compared with age-matched WKYs and was significantly worse in the 48-week-old SHR than the 24-week-old SHR. After pretreatments of phosphoinositide 3-kinase (PI3K) or NO synthase (NOS) inhibitors, the insulin- and IGF-1-mediated vasorelaxation became similar among four groups. The serum level of MDA was significantly increased, while the NO, catalase, and TAC were significantly reduced in the 48-week-old SHR compared with the 24-week-old SHR. This study demonstrated that the process of aging additively affected insulin- and IGF-1-mediated endothelial dysfunction in SHRs, which could be partly attributed to the reduced NO production and antioxidant deficiency.

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