Session 05 : Hypertension


Session 5: Hypertension
Chairpersons: Ritu Singh and Sagartirtha Sarkar

5:15-5:35 Ambuj Roy 
5:35-5:55 Madhu Anand Srivastava 
5:55-6:15 Ashok K. Srivastava 

Hypertension Burden: Trends from India

posted Jan 26, 2017, 1:22 AM by sourav ghosh   [ updated Jan 26, 2017, 11:45 PM ]

Ambuj Roy
All India Institute of Medical Science, New Delhi, India

High blood pressure is one of the leading risk factors for mortality in India. The prevalence of HBP has progressively increased in both rural and urban India over the last decades. On basis of two large cross-sectional study in rural and urban Delhi done 20 years apart, we found that the age and sex standardised prevalence of hypertension increased from 11 .2% to 28.9% (p<0.001) and 23.0% to 42.2% (p<0.001) in rural and urban NCR respectively. In both surveys, those with high education, alcohol use, obesity and high fasting blood glucose were at a higher risk for hypertension. However, the change in hypertension prevalence between the surveys was independent of these risks. Overall there was with no improvement in awareness, treatment and control rates of hypertension in the population. 

Gi Proteins and regulation of blood pressure

posted Jan 26, 2017, 1:21 AM by sourav ghosh

Madhu Anand-Srivastava
Department of Pharmacology and Physiology, University of Montreal, Montreal, Quebec, Canada

Guanine nucleotide regulatory proteins (G proteins) play an important role in the regulation of a variety of physiological functions including blood pressure through the activation of different effectors. Alterations in the levels of inhibitory G proteins (Gi) that negatively regulate adenylyl cyclase result in the impaired cellular functions that lead to various pathological states such as hypertension.. We have previously shown an overexpression of inhibitory G proteins (Gialpha proteins) in spontaneously hypertensive rats (SHR) and other models of hypertensive rats.The enhanced expression of Gialpha proteins precedes the development of hypertension in SHR and DOCA-salt hypertensive rats. Treatment of prehypertensive SHR with pertussis toxin that inactivates both Gialpha-2 and Gialpha-3 proteins prevented the development of hypertension in SHR suggesting the implication of enhanced expression of Gialpha proteins in the pathogenesis of hypertension.In the present study, we investigated if both the Gialpha-2 and Gialpha-3 proteins are implicated in the development of hypertension and used the antisense (AS) approach. The knockdown of Gialpha-2 protein by Gialpha-2 AS prevented the development of hypertension up to 6 weeks of age, thereafter it started increasing and reached the same level at 9 weeks as that of untreated SHR. On the other hand, the treatment of SHR with Gialpha-3 AS did not significantly attenuate the increased BP. Furthermore, the levels of Gialpha-2 and Gialpha-3 proteins in heart, kidney and aorta from 6 week-old SHR treated with Gialpha-2-AS and Gialpha-3-AS were significantly decreased compared to control SHR. However, these treatments did not attenuate the increased BP and overexpression of Gialpha-2 and Gialpha-3 proteins in 9 week-old SHR. Furthermore, treatment of prehypertensive SHR with C-ANP4-23; an agonist of natriuretic peptide receptor-C (NPR-C) and resveratrol, attenuated the development of hypertension and overexpression of Giα proteins in heart and aorta. These results suggestthat Gialpha-2 protein plays an important role in the development of hypertension in SHR and thatthe new therapies targeting Gialpha proteins may be developed for the treatment of hypertension (Supported by grant from CIHR).

Role of store-operated calcium entry in Angiotensin-II-induced expression of Egr-1 in vascular smooth muscle cells

posted Jan 26, 2017, 1:19 AM by sourav ghosh

Ashok K. Srivastava
Research Centre, Centre hospitalier de l’Université de Montréal , Montreal, Canada

An upregulation of Egr-1 expression has been reported in models of atherosclerosis and intimal hyperplasia and, various vasoactive peptides and growth promoting stimuli have been shown to induce the expression of Egr-1 in vascular smooth muscle cells (VSMC).Angiotensin-II (Ang-II) is a key vasoactive peptide that has been implicated in the pathogenesis of vascular diseases. Ang-II elevates intracellular Ca2+ through activation of the store-operated calcium entry (SOCE) involving an inositol-3-phosphate receptor (IP3R)-coupled depletion of endoplasmic reticular Ca2+ and a subsequent activation of the stromal interaction molecule 1 (STIM-1) /Orai-1 complex.However, the involvement of IP3R/STIM-1/Orai-1-Ca2+-dependent signaling in Egr-1 expression in VSMC remains unexplored. Therefore, in the present studies, we have examined the role of Ca2+ signaling in Ang-II-induced Egr-1 expression in VSMC and investigated the contribution of STIM-1 or Orai-1 in mediating this response. 2-aminoethoxydiphenyl borate (2-APB), a dual non-competitive antagonist of IP3R and inhibitor of SOCE, decreased Ang-II-induced Ca2+ release and attenuated Ang-II-induced enhanced expression of Egr-1 protein and mRNA levels. Egr-1 upregulation was also suppressed following blockade of calmodulin and CaMKII. Furthermore, RNA interference-mediated depletion of STIM-1 or Orai-1 attenuated Ang-II-induced Egr-1 expression as well as Ang-II-induced phosphorylation of ERK1/2and CREB. In addition, siRNA-induced silencing of CREB resulted in a reduction in the expression ofEgr-1 stimulated by Ang-II. In summary, our data demonstrate that Ang-II-induced Egr-1 expression is mediated by STIM-1/Orai-1/Ca2+-dependent ERK1/2 and CREB signaling pathways in A-10 VSMC. (Supported by CIHR).

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