Cardiovascular responses to cold exposure

Abstract

The prevalence of hypertension is increased in winter and in cold regions of the world. Cold temperatures make hypertension worse and trigger cardiovascular complications (stroke, myocardial infarction, heart failure, etc.). Chronic or intermittent exposure to cold causes hypertension and cardiac hypertrophy in animals. The purpose of this review is to provide the recent advances in the mechanistic investigation of cold-induced hypertension (CIH). Cold temperatures increase the activities of the sympathetic nervous system (SNS) and the renin-angiotensin system (RAS). The SNS initiates CIH via the RAS. Cold exposure suppresses the expression of eNOS and formation of NO, increases the production of endothelin-1 (ET-1), up-regulates ETA receptors, but down-regulates ETB receptors. The roles of these factors and their relations in CIH will be reviewed.

Figure 1

Effects of knockout of AT_1A receptor gene (AT_1A-KO) on the cold-induced increase in cardiac endothelin-1 production. The measurement was done in mice expose to cold (5°C) for 5 weeks. AT_1A-KO-Cold, AT_1A-KO mice exposed to cold (5±2°C); AT_1A-KO-Warm, AT_1A-KO mice maintained at room temperatures (warm, 25±2°C); WT-Cold, wild type mice maintained at cold; WT-Warm, wild type mice maintained at room temperatures (warm). ***p<0.001 vs the WT-Warm group. N=6.

Figure 2

Effects of RNAi inhibition of mineralocorticoid receptors (MR) on the cold-induced increase in cardiac ET_A receptor protein expression. The measurement was done in mice exposed to cold for 32 days. RNA interference (RNAi) is a molecular technique used to inhibit a target protein expression; siRNA, small interference RNA; MRshRNA-Cold, mice treated with short hairpin siRNA for MR and exposed to cold (5±2°C); ControlshRNA-Cold, mice treated with scrambled short hairpin siRNA sequence and exposed to cold; PBS-Cold, mice treated with phosphate buffered solution and exposed to cold; PBS-Warm, mice treated with PBS and maintained at room temperatures (warm, 25°C). ***p<0.001 vs the PBS-Warm group. N=6.

Figure 3

A diagram to explain the development of cold-induced hypertension (CIH). AT_1AR, angiotensin II type 1A receptor; ET-1, endothelin-1; ET_A Receptor, endothelin type A receptor; ET_B Receptor, endothelin type B receptor.