Genotypes of sarco(endo)plasmic reticulum Ca²⁺-dependent ATPase II gene in substrains of spontaneously hypertensive rats

Objective: To search for a genetic marker of the sarco(endo)plasmic reticulum Ca²⁺-dependent ATPase (SERCA) II gene in spontaneously hypertensive rats (SHRs) and to investigate differences in blood pressure and intracellular Ca²⁺ among some substrains of SHRs and Wistar-Kyoto (WKY) rats related to their SERCA II genotypes. Design and methods: The coding region of the SERCA II gene was sequenced in SHRs. Blood pressure and intracellular Ca²⁺ concentration ([Ca²⁺]_i) in platelets were measured in substrains of SHRs and WKY rats with different SERCA II genotypes. Results: A point mutation that provided restriction fragment length polymorphisms (RFLPs) by HindIII or SauI was found in the SERCA II gene. The polymerase chain reaction (PCR) products were digested by HindIII in SHR substrains and WKY-Kyoto rats, whereas they were digested by SauI in normotensive strains and SHR-Toho. Among SHR-Kyoto, SHR-Toho, WKY-Kyoto and WKY-Charles River, the substrains with the HindIII-digested SERCA II genotype showed slightly but significantly higher systolic blood pressure and augmented agonist-stimulated [Ca²⁺]_i than those with the SauI-digested genotype. Conclusions: RFLPs were found in the SERCA II gene. In the substrain analysis of SHRs and WKY rats, higher blood pressure and increased [Ca²⁺]_i were associated with the SERCA II genotype digested by HindIII. The SERCA II gene locus has the potential to contribute to the development of hypertension and abnormal intracellular Ca²⁺ metabolism in SHRs. These RFLPs in the SERCA II gene should be a useful genetic marker.