Recombinant inbred (RI) strains (Prague HXB/BXH set) represent a unique model that allows for permanent summation of genetic and physiological information as well as the study of age-dependent changes in phenotypes and/or gene regulation. This study compared blood pressure (BP) measured in adult animals of RI strains by radiotelemetry with BP values obtained in conscious rats of comparable age subjected to short-term carotid catheterization or with those obtained by direct carotid puncture under ether anesthesia (almost 20 years ago). After radiotelemetry recording, the contribution of major vasoactive systems to BP maintenance was studied by consecutive inhibition of the renin-angiotensin system (RAS), sympathetic nervous system (SNS), and nitric oxide synthase. We found highly significant interrelationships among baseline BP values obtained by radiotelemetry, carotid catheterization, or carotid puncture. This indicates considerable stability of RI strains over the course of their long existence, and confirms the reliability of BP values used for genetic studies performed in the past. Subsequent analysis of vasoactive system participation revealed the importance of SNS for the maintenance of BP, as determined by either radiotelemetry or catheterization. The BP of catheterized rats also correlated closely with acute captopril-induced BP changes, but this was not the case for rats measured by radiotelemetry. NO-dependent vasodilatation matched the BP effects of SNS and RAS in both measuring conditions. Residual BP (recorded at sodium nitroprusside–induced dilatation of resistance vessels) was also responsible for a significant portion of the BP variation in RI strains. Our study confirms the validity of RI strains for the further genetic and physiological research of hypertension.
Gill TJ III Smith GJ, Wissler RW, Kunz HW : The rat as an experimental animal. Science 1989; 245: 269–276.
Pravenec M, Klír P, Křen V, Zicha J, Kuneš J : An analysis of spontaneous hypertension in spontaneously hypertensive rats by means of new recombinant inbred strains. J Hypertens 1989; 17: 217–222.
Hamet P, Pausová Z, Dumas P, et al: Newborn and adult recombinant inbred strains: a tool to search for genetic determinants of target organ damage in hypertension. Kidney Int 1998; 53: 1488–1492.
Pravenec M, Křen V : Genetic analysis of complex cardio-vascular traits in the spontaneously hypertensive rat. Exp Physiol 2005; 90: 273–276.
Hübner N, Wallace CA, Zimdahl H, et al: Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease. Nat Genet 2005; 37: 243–253.
Kramer K, Kinter LB : Evaluation and applications of radio-telemetry in small laboratory animals. Physiol Genomics 2003; 13: 197–205.
Brockway BP, Mills PA, Azar SH : A new method for continuous chronic measurement and recording of blood pressure, heart rate and activity in the rat via radio-telemetry. Clin Exp Hypertens A 1991; 5: 885–895.
Anderson NH, Devlin AM, Graham D, et al: Telemetry for cardiovascular monitoring in a pharmacological study. New approaches to data analysis. Hypertension 1999; 33: 248–255.
Kurtz TW, Griffin K A, Bidani AK, Davisson RL, Hall JE : Recommendations for blood pressure measurement in humans and experimental animals. Part 2: Blood pressure measurement in experimental animals. A statement for professionals from the subcommittee of professional and public education of the American Heart Association Council on High Blood Pressure Research. Arterioscler Thromb Vasc Biol 2005; 25: e22–e33.
Kuneš J, Dobešová Z, Zicha J : Altered balance of main vasopressor and vasodepressor systems in rats with genetic hypertension and hypertriglyceridaemia. Clin Sci 2002; 102: 269–277.
Dobešová Z, Kuneš J, Zicha J : The altered balance between sympathetic nervous system and nitric oxide in salt hypertensive Dahl rats: ontogenetic and F2 hybrid studies. J Hypertens 2002; 20: 945–955.
Zicha J, Dobešová Z, Kuneš J : Relative deficiency of nitric oxide–dependent vasodilation in salt-hypertensive Dahl rats: the possible role of superoxide anions. J Hypertens 2001; 19: 247–254.
Hojná S, Kadlecová M, Dobešová Z, Valoušková V, Zicha J, Kuneš J : The participation of brain NO synthase in blood pressure control of adult spontaneously hypertensive rats. Mol Cell Biochem 2007; 297: 21–29.
Jirout M, Krěnová D, Křen V, et al: A new framework marker-based linkage map and SDPs for the rat HXB/BXH strain set. Mamm Genome 2003; 14: 537–546.
Pravenec M, Křen V, Křenová D, et al: HXB/Ipcv and BXH/Cub recombinant inbred strains of the rat: strain distribution patterns of 632 alleles. Folia Biol (Praha) 1999; 45: 203–215.
Pravenec M, Zídek V, Landa V, Šimáková M, Mlejnek P, Kazdová L : Genetic analysis of metabolic syndrome in the spontaneously hypertensive rat. Physiol Res 2004; 53 ( Suppl 1): S15–S22.
Minami N, Imai Y, Hashimoto J, Abe K : Contribution of vascular nitric oxide to basal blood pressure in conscious spontaneously hypertensive rats and normotensive Wistar Kyoto rats. Clin Sci 1995; 89: 177–182.
Snedecor GW, Cochran WG : Statistical Methods. Ames, Iowa State University Press, 1968, pp 258–298, 339–380.
Gill JS, Zezulka AV, Beevers DG, Davies P : Relation between initial blood pressure and its fall after the treatment. Lancet 1985; 1 ( 8428): 567–569.
Printz MP, Jirout M, Jaworski R, Alemayehu A, Křen V : HXB/BXH rat recombinant inbred strain platform: a newly enhanced tool for cardiovascular, behavioral, and developmental genetics and genomics. J Appl Physiol 2003; 94: 2510–2522.
Kuneš J, Křen V, Klír P, Zicha J, Pravenec M : Genetic determination of heart and kidney weights studied using a set of recombinant inbred strains: the relationship to blood pressure. J Hypertens 1990; 8: 1091–1095.
Bazil MK, Krulan C, Webb RL : Telemetric monitoring of cardiovascular parameters in conscious spontaneously hypertensive rats. J Cardiovasc Pharmacol 1993; 22: 897–905.
Van Vliet BN, Chafe LL, Antic V, Schnyder-Candrian S, Montani JP : Direct and indirect methods used to study arterial blood pressure. J Pharmacol Toxicol Methods 2000; 4: 361–373.
Chiueh CC, Kopin IJ : Hyperresponsivity of spontaneously hypertensive rat to indirect measurement of blood pressure. Am J Physiol Heart Circ Physiol 1978; 234: H690–H695.
Dobešová Z, Zicha J, Kuneš J : Newborn organ weight and spontaneous hypertension: recombinant inbred strain study. Clin Exp Hypertens 1997; 19: 403–415.
Burešová M, Zídek V, Musilová A, et al: Genetic relationship between placental and fetal weights and markers of the metabolic syndrome in rat recombinant inbred strains. Physiol Genomics 2006; 26: 226–231.
Hirano Y, Tsunoda M, Shimosawa T, Matsui H, Fujita T, Funatsu T : Suppression of catechol-O-methyltransferase activity through blunting of α2-adrenoceptor can explain hypertension in Dahl salt-sensitive rats. Hypertens Res 2007; 30: 269–278.
Kajimoto K, Hiura Y, Sumiya T, Yasui N, Okuda T, Iwai N : Exclusion of the catechol-O-methyltransferase gene from genes contributing to salt-sensitive hypertension in Dahl salt-sensitive rats. Hypertens Res 2007; 30: 459–467.