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Genetic and environmental factors may contribute to the pathogenesis of essential hypertension. To facilitate genetic studies of hypertension and renal disorders, we sought to clone novel genes from a modified, equalized kidney (MEK) cDNA library of a spontaneously hypertensive rat (SHR).A kidney cDNA library of an SHR was synthesized using the modified equalization method. Inserts of 350 random clones were amplified by polymerase chain reaction (PCR) and sequenced, of which 246 were presumably unknown after being compared against a nonredundant database in the GenBank. The cDNA ends of clone 38S were obtained by rapid amplification of cDNA ends, sequenced, and then analyzed with Translate, Prosite, Profile, SignalP, and TMpred programs.The full-length cDNA was 938 bp, and translated into a 182-amino acid protein. The deduced protein had a metallophosphoesterase domain, a signal peptide at its amino end, a protein kinase C phosphorylation site, and a transmembrane domain. Northern blot analysis revealed that this gene was expressed in the heart, brain, spleen, lungs, liver, skeletal muscles, kidneys and testes of Sprague-Dawley rats. A putative protein of Arabidopsis thaliana shares 62% homology with protein 38S, but the two proteins differ in terms of function and structure.Our results support that protein 38S is a novel membrane metallophosphoesterase, although its function in the kidneys remains to be elucidated. This study also demonstrates the feasibility of using PCR to clone novel genes from our MEK cDNA library.

A case-control study was carried out on 272 Chinese subjects over 40 years of age, including 157 hypertensives and 115 normotensives, to examine the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and blood pressure (BP) status. The I/D polymorphism of the ACE gene was identified by polymerase chain reaction. As a whole group, the difference of allele frequencies between normotensives and hypertensives was statistically significant (chi 2 = 4.46, P = 0.03; D/I odds = 1.46), while there was no difference in the genotype distribution (chi 2 = 3.95, P = 0.13). In a subgroup with elderly hypertension (age65), the frequencies of D-allele and DD genotype significantly increased (chi 2 = 4.43, P = 0.03 and chi 2 = 4.03, P = 0.08, respectively; D/I odds = 2.28). The association and relative risk increased further in the male gender (chi 2 = 6.65, P = 0.01 and chi 2 = 7.51, P = 0.02 respectively; D/I odds = 4.57 and DD/II odds = 12.00 respectively). The D-allele increased with age in the hypertensives, while the I-allele increased with age in normotensives. Thus, we conclude that the deletion polymorphism of the ACE gene is significantly associated with male elderly hypertension, at least in this Chinese population. This observation, if proved in a larger population, may have some implications for the prevention and treatment strategy for elderly hypertension.

Disturbances in lipid metabolism have been observed during the early phase of acute myocardial ischemia. Accumulation of fatty acids in and around the ischemic cardiac cells has been implicated to play a role in both contractile and electrophysiological abnormalities. Linolenic acid is an essential fatty acid and constitutes the phospholipid moiety of the cell membrane. The purpose of this work was to study the effects of linolenic acid on the heart using canine preparations. A direct left atrial injection was used as the route of administration because intravenous injections of linolenic acid inevitably cause pulmonary edema. A surface lead electrocardiogram (ECG), an epicardial electrogram, femoral arterial pressure, left ventricular pressure and its time derivative (dp/dt) were recorded before and after drug administration. Various dosages of linolenic acid (1 mg, 5 mg, 10 mg, 20 mg, 30 mg and 60 mg/kg) and a control buffer solution were tested. The results showed that linolenic acid has a potent dose-dependent bradycardic and myocardial depression effect starting from a dose of 5 mg/kg (delta HR = -20.1 +/- 4.0 bpm, delta dp/dt = 364.3 +/- 66.0 mmHg, sec-1, p less than 0.01 vs. control). At a high dose of 30 mg/kg, linolenic acid induced premature ventricular complexes. Furthermore, ventricular tachycardia was observed in 5 of the 8 dogs (62.5%) receiving the high dose of 60 mg/kg. We conclude that linolenic acid has profound effects on the canine heart; at a low dose, it causes bradycardia and myocardial depression, while at a high dose, it also produces ventricular irritability.