| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hypertension, Vol 21, 420-431, Copyright © 1993 by American Heart Association
CK Kost Jr and EK Jackson
Results from renal transplantation experiments demonstrate that a renal
defect is responsible for the development of hypertension in the
spontaneously hypertensive rat (SHR). In addition, studies with inhibitors
of the renin-angiotensin system have shown that angiotensin II (Ang II) is
required for the development and maintenance of hypertension in the SHR.
These observations prompted us to propose the hypothesis that hypertension
in these rats is due to an enhanced renal responsiveness to Ang II. The
purpose of the present study was to determine whether an enhanced renal
responsiveness to Ang II exists in adult (12- to 14-week-old) SHR relative
to Wistar-Kyoto control rats. To prevent hypertension-induced changes in
renal function in SHR, we maintained both strains in the normotensive state
from 4 weeks of age with long-term captopril treatment (100 mg/kg per day).
Intrarenal Ang II infusions induced a significantly greater decrease in
renal blood flow and glomerular filtration rate and a significantly greater
increase in renal vascular resistance in SHR compared with Wistar-Kyoto
rats. DuP 753 (Ang II subtype 1 [AT1] receptor antagonist), but not PD
123177 (Ang II subtype 2 receptor antagonist), blocked the renal responses
to Ang II in SHR, suggesting that the enhanced renal responsiveness to Ang
II was mediated solely by the AT1 receptor subtype. Unlike renal responses
to Ang II, renal responses to periarterial renal nerve stimulation were
similar in both strains, suggesting a selective renal hyperresponsiveness
to Ang II in the SHR rather than a general hyperresponsiveness toward all
vasoconstrictors. From these studies in chronically captopril-treated rats,
we conclude that 1) SHR have a genetically determined, enhanced renal
responsiveness to Ang II; 2) the enhanced renal responsiveness to Ang II is
mediated by the AT1 receptor; and 3) renal responses to periarterial nerve
stimulation are not significantly enhanced, suggesting a selective
hyperresponsiveness to Ang II in the kidneys of SHR.
ARTICLES
Enhanced renal angiotensin II subtype 1 receptor responses in the spontaneously hypertensive rat
Center for Clinical Pharmacology, University of Pittsburgh Medical Center, Pa. 15261.
This article has been cited by other articles:
 |
|
 |
|
  J. Song, K. M. Eyster, C. K. Kost Jr, B. Kjellsen, and D. S. Martin Involvement of protein kinase C-CPI-17 in androgen modulation of angiotensin II-renal vasoconstriction Cardiovasc Res, October 23, 2009; (2009) cvp326v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pedrosa, V. A. M. Villar, A. M. Pascua, S. Simao, U. Hopfer, P. A. Jose, and P. Soares-da-Silva H2O2 Stimulation of the Cl-/HCO3- Exchanger by Angiotensin II and Angiotensin II Type 1 Receptor Distribution in Membrane Microdomains Hypertension, May 1, 2008; 51(5): 1332 - 1338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Siddiqui and T. Hussain Enhanced AT1 receptor-mediated vasocontractile response to ANG II in endothelium-denuded aorta of obese Zucker rats Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1722 - H1727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Joly, R. Seqqat, B. Flamion, N. Caron, A. Michel, J. D. Imig, and R. Kramp Increased renal vascular reactivity to ANG II after unilateral nephrectomy in the rat involves 20-HETE Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2006; 291(4): R977 - R986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Dubinion, Z. Mi, and E. K. Jackson Role of Renal Sympathetic Nerves in Regulating Renovascular Responses to Angiotensin II in Spontaneously Hypertensive Rats J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1330 - 1336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Dubinion, Z. Mi, C. Zhu, L. Gao, and E. K. Jackson Pancreatic Polypeptide-Fold Peptide Receptors and Angiotensin II-Induced Renal Vasoconstriction Hypertension, March 1, 2006; 47(3): 545 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Jackson, L. Gao, and C. Zhu Mechanism of the Vascular Angiotensin II/{alpha}2-Adrenoceptor Interaction J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1109 - 1116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. C. Kopp and M. Z. Cicha Impaired substance P release from renal sensory nerves in SHR involves a pertussis toxin-sensitive mechanism Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R326 - R333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Jackson and W. A. Herzer Renal Extraction of Angiotensin II J. Pharmacol. Exp. Ther., December 1, 2003; 307(3): 1001 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gao, C. Zhu, and E. K. Jackson alpha 2-Adrenoceptors Potentiate Angiotensin II- and Vasopressin-Induced Renal Vasoconstriction in Spontaneously Hypertensive Rats J. Pharmacol. Exp. Ther., May 1, 2003; 305(2): 581 - 586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Jackson, W. A. Herzer, C. K. Kost Jr, and S. J. Vyas Enhanced Interaction Between Renovascular {alpha}2-Adrenoceptors and Angiotensin II Receptors in Genetic Hypertension Hypertension, September 1, 2001; 38(3): 353 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. W. Dukacz, M.-G. Feng, L.-F. Yang, R. M. K. W. Lee, and R. L. Kline Abnormal renal medullary response to angiotensin II in SHR is corrected by long-term enalapril treatment Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2001; 280(4): R1076 - R1084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. T. Andresen, E. K. Jackson, and G. G. Romero Angiotensin II Signaling to Phospholipase D in Renal Microvascular Smooth Muscle Cells in SHR Hypertension, February 1, 2001; 37(2): 635 - 639. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-C. Chen, J. L. Bouchie, A. S. Perez, A. C. Clermont, S. Izumo, J. Hampe, and E. P. Feener Role of the Angiotensin AT1 Receptor in Rat Aortic and Cardiac PAI-1 Gene Expression Arterioscler Thromb Vasc Biol, October 1, 2000; 20(10): 2297 - 2302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hines and W. A. Herzer Effect of cardiac receptor stimulation on renal vascular resistance in the pregnant rat Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2000; 278(1): R171 - R178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Jackson, W. A. Herzer, Z. Mi, S. J. Vyas, and C. K. Kost Jr Low-Dose Angiotensin II Reduces Urinary Cyclic AMP Excretion in Spontaneously Hypertensive, But Not Normotensive, Rats: Independence from Hypertension and Renal Hemodynamic Effects of Angiotensin J. Pharmacol. Exp. Ther., October 1, 1999; 291(1): 115 - 123. [Abstract] [Full Text]
|
|
|
|
|
|
E. K. Jackson, W. A. Herzer, S. J. Vyas, and C. K. Kost Jr Angiotensin II-Induced Renal Vasoconstriction in Genetic Hypertension J. Pharmacol. Exp. Ther., October 1, 1999; 291(1): 329 - 334. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. M. Jacinto, J. J. Mullins, and K. D. Mitchell Enhanced renal vascular responsiveness to angiotensin II in hypertensive ren-2 transgenic rats Am J Physiol Renal Physiol, February 1, 1999; 276(2): F315 - F322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Healy and L. Song Kidney Aminopeptidase A and Hypertension, Part I : Spontaneously Hypertensive Rats Hypertension, February 1, 1999; 33(2): 740 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-C. Fang and W.-C. Huang Angiotensin Receptor Blockade Blunts Hyperinsulinemia-Induced Hypertension in Rats Hypertension, August 1, 1998; 32(2): 235 - 242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Vyas, R. Mokkapatti, R. K. Dubey, M. R. Chinoy, and E. K. Jackson Guanine Nucleotide-Binding Inhibitory Protein-Mediated Inhibition of Adenylyl Cyclase Is Enhanced in Spontaneously Hypertensive Rat Preglomerular Arteriolar Smooth Muscle Cells J. Pharmacol. Exp. Ther., May 1, 1998; 285(2): 828 - 834. [Abstract] [Full Text]
|
|
|
|
|
|
R. Mokkapatti, S. J. Vyas, and E. K. Jackson G protein mRNA expression in renal microvessels from spontaneously hypertensive and Wistar-Kyoto rats Am J Physiol Renal Physiol, December 1, 1997; 273(6): F877 - F882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ichihara, E. W. Inscho, J. D. Imig, R. E. Michel, and L. G. Navar Role of Renal Nerves in Afferent Arteriolar Reactivity in Angiotensin-Induced Hypertension Hypertension, January 1, 1997; 29(1): 442 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Notoya, M. Nakamura, and K. Mizojiri Effects of Lisinopril on the Structure of Renal Arterioles Hypertension, March 1, 1996; 27(3): 364 - 370. [Abstract] [Full Text]
|
|
|
|
|
|
X. C. Li and R. E. Widdop Regional Hemodynamic Effects of the AT1 Receptor Antagonist CV-11974 in Conscious Renal Hypertensive Rats Hypertension, December 1, 1995; 26(6): 989 - 997. [Abstract] [Full Text]
|
|
|
|
|
|
J. Navarro-Cid, R. Maeso, F. Perez-Vizcaino, V. Cachofeiro, L. M. Ruilope, J. Tamargo, and V. Lahera Effects of Losartan on Blood Pressure, Metabolic Alterations, and Vascular Reactivity in the Fructose-Induced Hypertensive Rat Hypertension, December 1, 1995; 26(6): 1074 - 1078. [Abstract] [Full Text]
|
|
|
|
|
|
D. Rizzoni, M. Castellano, E. Porteri, G. Bettoni, M. L. Muiesan, A. Cinelli, and E. A. Rosei Effects of Low and High Doses of Fosinopril on the Structure and Function of Resistance Arteries Hypertension, July 1, 1995; 26(1): 118 - 123. [Abstract] [Full Text]
|
|
|
|
|
|
D. J. Campbell, A.-M. Duncan, A. Kladis, and S. B. Harrap Angiotensin Peptides in Spontaneously Hypertensive and Normotensive Donryu Rats Hypertension, May 1, 1995; 25(5): 928 - 934. [Abstract] [Full Text]
|
|